Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

PubMed

McNally, Elizabeth M; Puckelwartz, Megan J

2015-01-01

With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

Human Facial Shape and Size Heritability and Genetic Correlations.

PubMed

Cole, Joanne B; Manyama, Mange; Larson, Jacinda R; Liberton, Denise K; Ferrara, Tracey M; Riccardi, Sheri L; Li, Mao; Mio, Washington; Klein, Ophir D; Santorico, Stephanie A; Hallgrímsson, Benedikt; Spritz, Richard A

2017-02-01

The human face is an array of variable physical features that together make each of us unique and distinguishable. Striking familial facial similarities underscore a genetic component, but little is known of the genes that underlie facial shape differences. Numerous studies have estimated facial shape heritability using various methods. Here, we used advanced three-dimensional imaging technology and quantitative human genetics analysis to estimate narrow-sense heritability, heritability explained by common genetic variation, and pairwise genetic correlations of 38 measures of facial shape and size in normal African Bantu children from Tanzania. Specifically, we fit a linear mixed model of genetic relatedness between close and distant relatives to jointly estimate variance components that correspond to heritability explained by genome-wide common genetic variation and variance explained by uncaptured genetic variation, the sum representing total narrow-sense heritability. Our significant estimates for narrow-sense heritability of specific facial traits range from 28 to 67%, with horizontal measures being slightly more heritable than vertical or depth measures. Furthermore, for over half of facial traits, >90% of narrow-sense heritability can be explained by common genetic variation. We also find high absolute genetic correlation between most traits, indicating large overlap in underlying genetic loci. Not surprisingly, traits measured in the same physical orientation (i.e., both horizontal or both vertical) have high positive genetic correlations, whereas traits in opposite orientations have high negative correlations. The complex genetic architecture of facial shape informs our understanding of the intricate relationships among different facial features as well as overall facial development. Copyright © 2017 by the Genetics Society of America.

Genetic Architecture of Micro-Environmental Plasticity in Drosophila melanogaster.

PubMed

Morgante, Fabio; Sørensen, Peter; Sorensen, Daniel A; Maltecca, Christian; Mackay, Trudy F C

2015-05-06

Individuals of the same genotype do not have the same phenotype for quantitative traits when reared under common macro-environmental conditions, a phenomenon called micro-environmental plasticity. Genetic variation in micro-environmental plasticity is assumed in models of the evolution of phenotypic variance, and is important in applied breeding and personalized medicine. Here, we quantified genetic variation for micro-environmental plasticity for three quantitative traits in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel. We found substantial genetic variation for micro-environmental plasticity for all traits, with broad sense heritabilities of the same magnitude or greater than those of trait means. Micro-environmental plasticity is not correlated with residual segregating variation, is trait-specific, and has genetic correlations with trait means ranging from zero to near unity. We identified several candidate genes associated with micro-environmental plasticity of startle response, including Drosophila Hsp90, setting the stage for future genetic dissection of this phenomenon.

High levels of heterozygosity found for 15 SSR loci in Solanum chacoense

USDA-ARS?s Scientific Manuscript database

Genetic variation is a necessary prerequisite for improving domesticated plants through breeding; without it, breeding progress would be impossible. Genetic variation can be readily ascertained with co-dominant DNA markers, such as simple sequence repeats (SSRs). Twenty-four SSR markers specifically...

Genet-specific DNA methylation probabilities detected in a spatial epigenetic analysis of a clonal plant population.

PubMed

Araki, Kiwako S; Kubo, Takuya; Kudoh, Hiroshi

2017-01-01

In sessile organisms such as plants, spatial genetic structures of populations show long-lasting patterns. These structures have been analyzed across diverse taxa to understand the processes that determine the genetic makeup of organismal populations. For many sessile organisms that mainly propagate via clonal spread, epigenetic status can vary between clonal individuals in the absence of genetic changes. However, fewer previous studies have explored the epigenetic properties in comparison to the genetic properties of natural plant populations. Here, we report the simultaneous evaluation of the spatial structure of genetic and epigenetic variation in a natural population of the clonal plant Cardamine leucantha. We applied a hierarchical Bayesian model to evaluate the effects of membership of a genet (a group of individuals clonally derived from a single seed) and vegetation cover on the epigenetic variation between ramets (clonal plants that are physiologically independent individuals). We sampled 332 ramets in a 20 m × 20 m study plot that contained 137 genets (identified using eight SSR markers). We detected epigenetic variation in DNA methylation at 24 methylation-sensitive amplified fragment length polymorphism (MS-AFLP) loci. There were significant genet effects at all 24 MS-AFLP loci in the distribution of subepiloci. Vegetation cover had no statistically significant effect on variation in the majority of MS-AFLP loci. The spatial aggregation of epigenetic variation is therefore largely explained by the aggregation of ramets that belong to the same genets. By applying hierarchical Bayesian analyses, we successfully identified a number of genet-specific changes in epigenetic status within a natural plant population in a complex context, where genotypes and environmental factors are unevenly distributed. This finding suggests that it requires further studies on the spatial epigenetic structure of natural populations of diverse organisms, particularly for sessile clonal species.

The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

PubMed

Auld, Stuart K J R; Edel, Kai H; Little, Tom J

2012-10-01

In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

The first Malay database toward the ethnic-specific target molecular variation.

PubMed

Halim-Fikri, Hashim; Etemad, Ali; Abdul Latif, Ahmad Zubaidi; Merican, Amir Feisal; Baig, Atif Amin; Annuar, Azlina Ahmad; Ismail, Endom; Salahshourifar, Iman; Liza-Sharmini, Ahmad Tajudin; Ramli, Marini; Shah, Mohamed Irwan; Johan, Muhammad Farid; Hassan, Nik Norliza Nik; Abdul-Aziz, Noraishah Mydin; Mohd Noor, Noor Haslina; Nur-Shafawati, Ab Rajab; Hassan, Rosline; Bahar, Rosnah; Zain, Rosnah Binti; Yusoff, Shafini Mohamed; Yusoff, Surini; Tan, Soon Guan; Thong, Meow-Keong; Wan-Isa, Hatin; Abdullah, Wan Zaidah; Mohamed, Zahurin; Abdul Latiff, Zarina; Zilfalil, Bin Alwi

2015-04-30

The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.

Genetic variation in adaptability and pleiotropy in budding yeast

PubMed Central

Mitchell, James Kameron; Bloom, Joshua S; Kruglyak, Leonid

2017-01-01

Evolution can favor organisms that are more adaptable, provided that genetic variation in adaptability exists. Here, we quantify this variation among 230 offspring of a cross between diverged yeast strains. We measure the adaptability of each offspring genotype, defined as its average rate of adaptation in a specific environmental condition, and analyze the heritability, predictability, and genetic basis of this trait. We find that initial genotype strongly affects adaptability and can alter the genetic basis of future evolution. Initial genotype also affects the pleiotropic consequences of adaptation for fitness in a different environment. This genetic variation in adaptability and pleiotropy is largely determined by initial fitness, according to a rule of declining adaptability with increasing initial fitness, but several individual QTLs also have a significant idiosyncratic role. Our results demonstrate that both adaptability and pleiotropy are complex traits, with extensive heritable differences arising from naturally occurring variation. PMID:28826486

Host-parasite coevolution: genetic variation in a virus population and the interaction with a host gene.

PubMed

Wilfert, L; Jiggins, F M

2010-07-01

Host-parasite coevolution is considered to be an important factor in maintaining genetic variation in resistance to pathogens. Drosophila melanogaster is naturally infected by the sigma virus, a vertically transmitted and host-specific pathogen. In fly populations, there is a large amount of genetic variation in the transmission rate from parent to offspring, much of which is caused by major-effect resistance polymorphisms. We have found that there are similarly high levels of genetic variation in the rate of paternal transmission among 95 different isolates of the virus as in the host. However, when we examined a transmission-blocking gene in the host, we found that it was effective across virus isolates. Therefore, the high levels of genetic variation observed in this system do not appear to be maintained because of coevolution resulting from interactions between this host gene and parasite genes.

Genetic variation in adaptability and pleiotropy in budding yeast.

PubMed

Jerison, Elizabeth R; Kryazhimskiy, Sergey; Mitchell, James Kameron; Bloom, Joshua S; Kruglyak, Leonid; Desai, Michael M

2017-08-17

Evolution can favor organisms that are more adaptable, provided that genetic variation in adaptability exists. Here, we quantify this variation among 230 offspring of a cross between diverged yeast strains. We measure the adaptability of each offspring genotype, defined as its average rate of adaptation in a specific environmental condition, and analyze the heritability, predictability, and genetic basis of this trait. We find that initial genotype strongly affects adaptability and can alter the genetic basis of future evolution. Initial genotype also affects the pleiotropic consequences of adaptation for fitness in a different environment. This genetic variation in adaptability and pleiotropy is largely determined by initial fitness, according to a rule of declining adaptability with increasing initial fitness, but several individual QTLs also have a significant idiosyncratic role. Our results demonstrate that both adaptability and pleiotropy are complex traits, with extensive heritable differences arising from naturally occurring variation.

Genetic and epigenetic differences associated with environmental gradients in replicate populations of two salt marsh perennials.

PubMed

Foust, C M; Preite, V; Schrey, A W; Alvarez, M; Robertson, M H; Verhoeven, K J F; Richards, C L

2016-04-01

While traits and trait plasticity are partly genetically based, investigating epigenetic mechanisms may provide more nuanced understanding of the mechanisms underlying response to environment. Using AFLP and methylation-sensitive AFLP, we tested the hypothesis that differentiation to habitats along natural salt marsh environmental gradients occurs at epigenetic, but not genetic loci in two salt marsh perennials. We detected significant genetic and epigenetic structure among populations and among subpopulations, but we found multilocus patterns of differentiation to habitat type only in epigenetic variation for both species. In addition, more epigenetic than genetic loci were correlated with habitat in both species. When we analysed genetic and epigenetic variation simultaneously with partial Mantel, we found no correlation between genetic variation and habitat and a significant correlation between epigenetic variation and habitat in Spartina alterniflora. In Borrichia frutescens, we found significant correlations between epigenetic and/or genetic variation and habitat in four of five populations when populations were analysed individually, but there was no significant correlation between genetic or epigenetic variation and habitat when analysed jointly across the five populations. These analyses suggest that epigenetic mechanisms are involved in the response to salt marsh habitats, but also that the relationships among genetic and epigenetic variation and habitat vary by species. Site-specific conditions may also cloud our ability to detect response in replicate populations with similar environmental gradients. Future studies analysing sequence data and the correlation between genetic variation and DNA methylation will be powerful to identify the contributions of genetic and epigenetic response to environmental gradients. © 2016 John Wiley & Sons Ltd.

Genetic effects on gene expression across human tissues

PubMed Central

2017-01-01

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease. PMID:29022597

Genetic effects on gene expression across human tissues.

PubMed

Battle, Alexis; Brown, Christopher D; Engelhardt, Barbara E; Montgomery, Stephen B

2017-10-11

Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of disease.

Genetic Architectures of Quantitative Variation in RNA Editing Pathways

PubMed Central

Gu, Tongjun; Gatti, Daniel M.; Srivastava, Anuj; Snyder, Elizabeth M.; Raghupathy, Narayanan; Simecek, Petr; Svenson, Karen L.; Dotu, Ivan; Chuang, Jeffrey H.; Keller, Mark P.; Attie, Alan D.; Braun, Robert E.; Churchill, Gary A.

2016-01-01

RNA editing refers to post-transcriptional processes that alter the base sequence of RNA. Recently, hundreds of new RNA editing targets have been reported. However, the mechanisms that determine the specificity and degree of editing are not well understood. We examined quantitative variation of site-specific editing in a genetically diverse multiparent population, Diversity Outbred mice, and mapped polymorphic loci that alter editing ratios globally for C-to-U editing and at specific sites for A-to-I editing. An allelic series in the C-to-U editing enzyme Apobec1 influences the editing efficiency of Apob and 58 additional C-to-U editing targets. We identified 49 A-to-I editing sites with polymorphisms in the edited transcript that alter editing efficiency. In contrast to the shared genetic control of C-to-U editing, most of the variable A-to-I editing sites were determined by local nucleotide polymorphisms in proximity to the editing site in the RNA secondary structure. Our results indicate that RNA editing is a quantitative trait subject to genetic variation and that evolutionary constraints have given rise to distinct genetic architectures in the two canonical types of RNA editing. PMID:26614740

Evolutionary implications of mitochondrial genetic variation: mitochondrial genetic effects on OXPHOS respiration and mitochondrial quantity change with age and sex in fruit flies.

PubMed

Wolff, J N; Pichaud, N; Camus, M F; Côté, G; Blier, P U; Dowling, D K

2016-04-01

The ancient acquisition of the mitochondrion into the ancestor of modern-day eukaryotes is thought to have been pivotal in facilitating the evolution of complex life. Mitochondria retain their own diminutive genome, with mitochondrial genes encoding core subunits involved in oxidative phosphorylation. Traditionally, it was assumed that there was little scope for genetic variation to accumulate and be maintained within the mitochondrial genome. However, in the past decade, mitochondrial genetic variation has been routinely tied to the expression of life-history traits such as fertility, development and longevity. To examine whether these broad-scale effects on life-history trait expression might ultimately find their root in mitochondrially mediated effects on core bioenergetic function, we measured the effects of genetic variation across twelve different mitochondrial haplotypes on respiratory capacity and mitochondrial quantity in the fruit fly, Drosophila melanogaster. We used strains of flies that differed only in their mitochondrial haplotype, and tested each sex separately at two different adult ages. Mitochondrial haplotypes affected both respiratory capacity and mitochondrial quantity. However, these effects were highly context-dependent, with the genetic effects contingent on both the sex and the age of the flies. These sex- and age-specific genetic effects are likely to resonate across the entire organismal life-history, providing insights into how mitochondrial genetic variation may contribute to sex-specific trajectories of life-history evolution. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

The systematics and population genetics of Opisthorchis viverrini sensu lato: implications in parasite epidemiology and bile duct cancer.

PubMed

Sithithaworn, Paiboon; Andrews, Ross H; Petney, Trevor N; Saijuntha, Weerachai; Laoprom, Nonglak

2012-03-01

Together with host and environmental factors, the systematics and population genetic variation of Opisthorchis viverrini may contribute to recorded local and regional differences in epidemiology and host morbidity in opisthorchiasis and cholangiocarcinoma (CCA). In this review, we address recent findings that O. viverrini comprises a species complex with varying degrees of population genetic variation which are associated with specific river wetland systems within Thailand as well as the Lao PDR. Having an accurate understanding of systematics is a prerequisite for a meaningful assessment of the population structure of each species within the O. viverrini complex in nature, as well as a better understanding of the magnitude of genetic variation that occurs within different species of hosts in its life cycle. Whether specific genotypes are related to habitat type(s) and/or specific intermediate host species are discussed based on current available data. Most importantly, we focus on whether there is a correlation between incidence of CCA and genotype(s) of O. viverrini. This will provide a solid basis for further comprehensive investigations of the role of genetic variation within each species of O. viverrini sensu lato in human epidemiology and genotype related morbidity as well as co-evolution of parasites with primary and secondary intermediate species of host. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Epigenetic differentiation and relationship to adaptive genetic divergence in discrete populations of the violet Viola cazorlensis.

PubMed

Herrera, Carlos M; Bazaga, Pilar

2010-08-01

*In plants, epigenetic variations based on DNA methylation are often heritable and could influence the course of evolution. Before this hypothesis can be assessed, fundamental questions about epigenetic variation remain to be addressed in a real-world context, including its magnitude, structuring within and among natural populations, and autonomy in relation to the genetic context. *Extent and patterns of cytosine methylation, and the relationship to adaptive genetic divergence between populations, were investigated for wild populations of the southern Spanish violet Viola cazorlensis (Violaceae) using the methylation-sensitive amplified polymorphism (MSAP) technique, a modification of the amplified fragment length polymorphism method (AFLP) based on the differential sensitivity of isoschizomeric restriction enzymes to site-specific cytosine methylation. *The genome of V. cazorlensis plants exhibited extensive levels of methylation, and methylation-based epigenetic variation was structured into distinct between- and within- population components. Epigenetic differentiation of populations was correlated with adaptive genetic divergence revealed by a Bayesian population-genomic analysis of AFLP data. Significant associations existed at the individual genome level between adaptive AFLP loci and the methylation state of methylation-susceptible MSAP loci. *Population-specific, divergent patterns of correlated selection on epigenetic and genetic individual variation could account for the coordinated epigenetic-genetic adaptive population differentiation revealed by this study.

Direct and indirect genetic and fine-scale location effects on breeding date in song sparrows.

PubMed

Germain, Ryan R; Wolak, Matthew E; Arcese, Peter; Losdat, Sylvain; Reid, Jane M

2016-11-01

Quantifying direct and indirect genetic effects of interacting females and males on variation in jointly expressed life-history traits is central to predicting microevolutionary dynamics. However, accurately estimating sex-specific additive genetic variances in such traits remains difficult in wild populations, especially if related individuals inhabit similar fine-scale environments. Breeding date is a key life-history trait that responds to environmental phenology and mediates individual and population responses to environmental change. However, no studies have estimated female (direct) and male (indirect) additive genetic and inbreeding effects on breeding date, and estimated the cross-sex genetic correlation, while simultaneously accounting for fine-scale environmental effects of breeding locations, impeding prediction of microevolutionary dynamics. We fitted animal models to 38 years of song sparrow (Melospiza melodia) phenology and pedigree data to estimate sex-specific additive genetic variances in breeding date, and the cross-sex genetic correlation, thereby estimating the total additive genetic variance while simultaneously estimating sex-specific inbreeding depression. We further fitted three forms of spatial animal model to explicitly estimate variance in breeding date attributable to breeding location, overlap among breeding locations and spatial autocorrelation. We thereby quantified fine-scale location variances in breeding date and quantified the degree to which estimating such variances affected the estimated additive genetic variances. The non-spatial animal model estimated nonzero female and male additive genetic variances in breeding date (sex-specific heritabilities: 0·07 and 0·02, respectively) and a strong, positive cross-sex genetic correlation (0·99), creating substantial total additive genetic variance (0·18). Breeding date varied with female, but not male inbreeding coefficient, revealing direct, but not indirect, inbreeding depression. All three spatial animal models estimated small location variance in breeding date, but because relatedness and breeding location were virtually uncorrelated, modelling location variance did not alter the estimated additive genetic variances. Our results show that sex-specific additive genetic effects on breeding date can be strongly positively correlated, which would affect any predicted rates of microevolutionary change in response to sexually antagonistic or congruent selection. Further, we show that inbreeding effects on breeding date can also be sex specific and that genetic effects can exceed phenotypic variation stemming from fine-scale location-based variation within a wild population. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Genetic Architecture of Micro-Environmental Plasticity in Drosophila melanogaster

PubMed Central

Morgante, Fabio; Sørensen, Peter; Sorensen, Daniel A.; Maltecca, Christian; Mackay, Trudy F. C.

2015-01-01

Individuals of the same genotype do not have the same phenotype for quantitative traits when reared under common macro-environmental conditions, a phenomenon called micro-environmental plasticity. Genetic variation in micro-environmental plasticity is assumed in models of the evolution of phenotypic variance, and is important in applied breeding and personalized medicine. Here, we quantified genetic variation for micro-environmental plasticity for three quantitative traits in the inbred, sequenced lines of the Drosophila melanogaster Genetic Reference Panel. We found substantial genetic variation for micro-environmental plasticity for all traits, with broad sense heritabilities of the same magnitude or greater than those of trait means. Micro-environmental plasticity is not correlated with residual segregating variation, is trait-specific, and has genetic correlations with trait means ranging from zero to near unity. We identified several candidate genes associated with micro-environmental plasticity of startle response, including Drosophila Hsp90, setting the stage for future genetic dissection of this phenomenon. PMID:25943032

Host genetic variation impacts microbiome composition across human body sites.

PubMed

Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

2015-09-15

The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

Causal Genetic Variation Underlying Metabolome Differences.

PubMed

Swain-Lenz, Devjanee; Nikolskiy, Igor; Cheng, Jiye; Sudarsanam, Priya; Nayler, Darcy; Staller, Max V; Cohen, Barak A

2017-08-01

An ongoing challenge in biology is to predict the phenotypes of individuals from their genotypes. Genetic variants that cause disease often change an individual's total metabolite profile, or metabolome. In light of our extensive knowledge of metabolic pathways, genetic variants that alter the metabolome may help predict novel phenotypes. To link genetic variants to changes in the metabolome, we studied natural variation in the yeast Saccharomyces cerevisiae We used an untargeted mass spectrometry method to identify dozens of metabolite Quantitative Trait Loci (mQTL), genomic regions containing genetic variation that control differences in metabolite levels between individuals. We mapped differences in urea cycle metabolites to genetic variation in specific genes known to regulate amino acid biosynthesis. Our functional assays reveal that genetic variation in two genes, AUA1 and ARG81 , cause the differences in the abundance of several urea cycle metabolites. Based on knowledge of the urea cycle, we predicted and then validated a new phenotype: sensitivity to a particular class of amino acid isomers. Our results are a proof-of-concept that untargeted mass spectrometry can reveal links between natural genetic variants and metabolome diversity. The interpretability of our results demonstrates the promise of using genetic variants underlying natural differences in the metabolome to predict novel phenotypes from genotype. Copyright © 2017 by the Genetics Society of America.

Genetic approaches in comparative and evolutionary physiology

PubMed Central

Bridgham, Jamie T.; Kelly, Scott A.; Garland, Theodore

2015-01-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. PMID:26041111

Genetic approaches in comparative and evolutionary physiology.

PubMed

Storz, Jay F; Bridgham, Jamie T; Kelly, Scott A; Garland, Theodore

2015-08-01

Whole animal physiological performance is highly polygenic and highly plastic, and the same is generally true for the many subordinate traits that underlie performance capacities. Quantitative genetics, therefore, provides an appropriate framework for the analysis of physiological phenotypes and can be used to infer the microevolutionary processes that have shaped patterns of trait variation within and among species. In cases where specific genes are known to contribute to variation in physiological traits, analyses of intraspecific polymorphism and interspecific divergence can reveal molecular mechanisms of functional evolution and can provide insights into the possible adaptive significance of observed sequence changes. In this review, we explain how the tools and theory of quantitative genetics, population genetics, and molecular evolution can inform our understanding of mechanism and process in physiological evolution. For example, lab-based studies of polygenic inheritance can be integrated with field-based studies of trait variation and survivorship to measure selection in the wild, thereby providing direct insights into the adaptive significance of physiological variation. Analyses of quantitative genetic variation in selection experiments can be used to probe interrelationships among traits and the genetic basis of physiological trade-offs and constraints. We review approaches for characterizing the genetic architecture of physiological traits, including linkage mapping and association mapping, and systems approaches for dissecting intermediary steps in the chain of causation between genotype and phenotype. We also discuss the promise and limitations of population genomic approaches for inferring adaptation at specific loci. We end by highlighting the role of organismal physiology in the functional synthesis of evolutionary biology. Copyright © 2015 the American Physiological Society.

The genetic diversity and epizootiology of infectious hematopoietic necrosis virus

USGS Publications Warehouse

Oshima, Kevin H.; Arakawa, Cindy K.; Higman, Keith H.; Landolt, Marsha L.; Nichol, Stuart T.; Winton, James R.

1994-01-01

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which causes a serious disease in salmondd fish. The T1 ribonuclease fingerprinttin method was used to compare the RNA genomes of 26 isolates of IHNV recovered from sockeye salmon (Oncorhynchus nerka), chinook salmon (O. tshawytscha), and steelhead trout (O. mykiss) throughout the enzootic portion of western North America. Most of the isolates as a source of genetic variation. In from a single year (1987) to limit time of isolation as a source of genetic variation. In addition, isolates from different years collected at three sites were analyzed to investigate genetic drift or evolution of IHNV within specific locations. All of the isolates examined by T1 fingerprint analysis contained less than a 50% variation in spot location and were represented by a single fingerprint group. The observed variation was estimated to correspond to less than 5% variation in the nucleic acid sequence. However, sufficient variation was detected to separate the isolates into four subgroups which appeared to correlate to different geographic regions. Host species appeared not to be a significant source of variation. The evolutionary and epizootiologic significance of these findings and their relationship to other evidence of genetic variation in IHNV isolates are discussed.

Association of genetic and phenotypic variability with geography and climate in three southern California oaks.

PubMed

Riordan, Erin C; Gugger, Paul F; Ortego, Joaquín; Smith, Carrie; Gaddis, Keith; Thompson, Pam; Sork, Victoria L

2016-01-01

Geography and climate shape the distribution of organisms, their genotypes, and their phenotypes. To understand historical and future evolutionary and ecological responses to climate, we compared the association of geography and climate of three oak species (Quercus engelmannii, Quercus berberidifolia, and Quercus cornelius-mulleri) in an environmentally heterogeneous region of southern California at three organizational levels: regional species distributions, genetic variation, and phenotypic variation. We identified climatic variables influencing regional distribution patterns using species distribution models (SDMs), and then tested whether those individual variables are important in shaping genetic (microsatellite) and phenotypic (leaf morphology) variation. We estimated the relative contributions of geography and climate using multivariate redundancy analyses (RDA) with variance partitioning. The modeled distribution of each species was influenced by climate differently. Our analysis of genetic variation using RDA identified small but significant associations between genetic variation with climate and geography in Q. engelmannii and Q. cornelius-mulleri, but not in Q. berberidifolia, and climate explained more of the variation. Our analysis of phenotypic variation in Q. engelmannii indicated that climate had more impact than geography, but not in Q. berberidifolia. Throughout our analyses, we did not find a consistent pattern in effects of individual climatic variables. Our comparative analysis illustrates that climate influences tree response at all organizational levels, but the important climate factors vary depending on the level and on the species. Because of these species-specific and level-specific responses, today's sympatric species are unlikely to have similar distributions in the future. © 2016 Botanical Society of America.

Evidence of a genetic link between endometriosis and ovarian cancer.

PubMed

Lee, Alice W; Templeman, Claire; Stram, Douglas A; Beesley, Jonathan; Tyrer, Jonathan; Berchuck, Andrew; Pharoah, Paul P; Chenevix-Trench, Georgia; Pearce, Celeste Leigh

2016-01-01

To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. Pooled genetic analysis. University hospital. Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. None. Endometriosis-associated genetic variation and ovarian cancer. There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions. Copyright © 2016. Published by Elsevier Inc.

Molecular Darwinism: The Contingency of Spontaneous Genetic Variation

PubMed Central

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions. PMID:21979160

Molecular Darwinism: the contingency of spontaneous genetic variation.

PubMed

Arber, Werner

2011-01-01

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

Calpastatin and µ-calpain differ in their control of genotype specific residual variance of beef tenderness in Angus and MARC III steers

USDA-ARS?s Scientific Manuscript database

Genotype variant effects of calpastatin (CAST) and µ-calpain (CAPN1) on mean beef tenderness have been widely characterized. We have tested whether these genetic variants also control residual (non-genetic) variation, and subsequently total phenotypic variation, of tenderness. Observation of rare ...

Microevolution due to pollution in amphibians: A review on the genetic erosion hypothesis.

PubMed

Fasola, E; Ribeiro, R; Lopes, I

2015-09-01

The loss of genetic diversity, due to exposure to chemical contamination (genetic erosion), is a major threat to population viability. Genetic erosion is the loss of genetic variation: the loss of alleles determining the value of a specific trait or set of traits. Almost a third of the known amphibian species is considered to be endangered and a decrease of genetic variability can push them to the verge of extinction. This review indicates that loss of genetic variation due to chemical contamination has effects on: 1) fitness, 2) environmental plasticity, 3) co-tolerance mechanisms, 4) trade-off mechanisms, and 5) tolerance to pathogens in amphibian populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathogenesis of autism: a patchwork of genetic causes

PubMed Central

Grigorenko, Elena L

2009-01-01

Autism spectrum disorders (ASDs) are relatively infrequent but are devastating developmental conditions characterized by marked deficiencies in social, communicative and other behavioral domains. It has been known for a substantial period of time that these disorders are genetic in nature. However, elucidating the specific mechanisms of these disorders has been difficult. A major reason for such difficulty is the recognized genetic heterogeneity of ASDs. Specifically, many genetic mechanisms related to structural variations in the genome have been reported as possible genetic causes of these disorders. This review briefly exemplifies these genetic mechanisms, presents a concise overview of the evidence for the genetic basis of ASDs and provides an appraisal of the specific structural genetic variants thought to contribute to the pathogenesis of these complex disorders. PMID:19953194

Heritability and genetic covariation of sensitivity to PROP, SOA, quinine HCl, and caffeine.

PubMed

Hansen, Jonathan L; Reed, Danielle R; Wright, Margaret J; Martin, Nicholas G; Breslin, Paul A S

2006-06-01

The perceived bitterness intensity for bitter solutions of propylthiouracil (PROP), sucrose octa-acetate (SOA), quinine HCl and caffeine were examined in a genetically informative sample of 392 females and 313 males (mean age of 17.8 +/- 3.1 years), including 62 monozygotic and 131 dizygotic twin pairs and 237 sib pairs. Broad-sense heritabilities were estimated at 0.72, 0.28, 0.34, and 0.30 for PROP, SOA, quinine, and caffeine, respectively, for perceived intensity measures. Modeling showed 1) a group factor which explained a large amount of the genetic variation in SOA, quinine, and caffeine (22-28% phenotypic variation), 2) a factor responsible for all the genetic variation in PROP (72% phenotypic variation), which only accounted for 1% and 2% of the phenotypic variation in SOA and caffeine, respectively, and 3) a modest specific genetic factor for quinine (12% phenotypic variation). Unique environmental influences for all four compounds were due to a single factor responsible for 7-22% of phenotypic variation. The results suggest that the perception of PROP and the perception of SOA, quinine, and caffeine are influenced by two distinct sets of genes.

Heritability and Genetic Covariation of Sensitivity to PROP, SOA, Quinine HCl, and Caffeine

PubMed Central

Hansen, Jonathan L.; Reed, Danielle R.; Wright, Margaret J.; Martin, Nicholas G.; Breslin, Paul A. S.

2006-01-01

The perceived bitterness intensity for bitter solutions of propylthiouracil (PROP), sucrose octa-acetate (SOA), quinine HCl and caffeine were examined in a genetically informative sample of 392 females and 313 males (mean age of 17.8 ± 3.1 years), including 62 MZ and 131 DZ twin pairs and 237 sib pairs. Broad-sense heritabilities were estimated at 0.72, 0.28, 0.34, and 0.30 for PROP, SOA, quinine, and caffeine, respectively, for perceived intensity measures. Modeling showed 1) a group factor which explained a large amount of the genetic variation in SOA, quinine, and caffeine (22–28% phenotypic variation), 2) a factor responsible for all the genetic variation in PROP (72% phenotypic variation), which only accounted for 1% and 2% of the phenotypic variation in SOA and caffeine, respectively, and 3) a modest specific genetic factor for quinine (12% phenotypic variation). Unique environmental influences for all four compounds were due to a single factor responsible for 7–22% of phenotypic variation. The results suggest that the perception of PROP and the perception of SOA, quinine, and caffeine are influenced by two distinct sets of genes. PMID:16527870

Allele-specific gene expression in a wild nonhuman primate population

PubMed Central

Tung, J.; Akinyi, M. Y.; Mutura, S.; Altmann, J.; Wray, G. A.; Alberts, S. C.

2015-01-01

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual’s mother during its early life (an aspect of that individual’s social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals. PMID:21226779

Discovering Condition-Specific Gene Co-Expression Patterns Using Gaussian Mixture Models: A Cancer Case Study.

PubMed

Ficklin, Stephen P; Dunwoodie, Leland J; Poehlman, William L; Watson, Christopher; Roche, Kimberly E; Feltus, F Alex

2017-08-17

A gene co-expression network (GCN) describes associations between genes and points to genetic coordination of biochemical pathways. However, genetic correlations in a GCN are only detectable if they are present in the sampled conditions. With the increasing quantity of gene expression samples available in public repositories, there is greater potential for discovery of genetic correlations from a variety of biologically interesting conditions. However, even if gene correlations are present, their discovery can be masked by noise. Noise is introduced from natural variation (intrinsic and extrinsic), systematic variation (caused by sample measurement protocols and instruments), and algorithmic and statistical variation created by selection of data processing tools. A variety of published studies, approaches and methods attempt to address each of these contributions of variation to reduce noise. Here we describe an approach using Gaussian Mixture Models (GMMs) to address natural extrinsic (condition-specific) variation during network construction from mixed input conditions. To demonstrate utility, we build and analyze a condition-annotated GCN from a compendium of 2,016 mixed gene expression data sets from five tumor subtypes obtained from The Cancer Genome Atlas. Our results show that GMMs help discover tumor subtype specific gene co-expression patterns (modules) that are significantly enriched for clinical attributes.

Climate variables explain neutral and adaptive variation within salmonid metapopulations: The importance of replication in landscape genetics

USGS Publications Warehouse

Hand, Brian K.; Muhlfeld, Clint C.; Wade, Alisa A.; Kovach, Ryan; Whited, Diane C.; Narum, Shawn R.; Matala, Andrew P.; Ackerman, Michael W.; Garner, B. A.; Kimball, John S; Stanford, Jack A.; Luikart, Gordon

2016-01-01

Understanding how environmental variation influences population genetic structure is important for conservation management because it can reveal how human stressors influence population connectivity, genetic diversity and persistence. We used riverscape genetics modelling to assess whether climatic and habitat variables were related to neutral and adaptive patterns of genetic differentiation (population-specific and pairwise FST) within five metapopulations (79 populations, 4583 individuals) of steelhead trout (Oncorhynchus mykiss) in the Columbia River Basin, USA. Using 151 putatively neutral and 29 candidate adaptive SNP loci, we found that climate-related variables (winter precipitation, summer maximum temperature, winter highest 5% flow events and summer mean flow) best explained neutral and adaptive patterns of genetic differentiation within metapopulations, suggesting that climatic variation likely influences both demography (neutral variation) and local adaptation (adaptive variation). However, we did not observe consistent relationships between climate variables and FST across all metapopulations, underscoring the need for replication when extrapolating results from one scale to another (e.g. basin-wide to the metapopulation scale). Sensitivity analysis (leave-one-population-out) revealed consistent relationships between climate variables and FST within three metapopulations; however, these patterns were not consistent in two metapopulations likely due to small sample sizes (N = 10). These results provide correlative evidence that climatic variation has shaped the genetic structure of steelhead populations and highlight the need for replication and sensitivity analyses in land and riverscape genetics.

Population and allelic variation of A-to-I RNA editing in human transcriptomes.

PubMed

Park, Eddie; Guo, Jiguang; Shen, Shihao; Demirdjian, Levon; Wu, Ying Nian; Lin, Lan; Xing, Yi

2017-07-28

A-to-I RNA editing is an important step in RNA processing in which specific adenosines in some RNA molecules are post-transcriptionally modified to inosines. RNA editing has emerged as a widespread mechanism for generating transcriptome diversity. However, there remain significant knowledge gaps about the variation and function of RNA editing. In order to determine the influence of genetic variation on A-to-I RNA editing, we integrate genomic and transcriptomic data from 445 human lymphoblastoid cell lines by combining an RNA editing QTL (edQTL) analysis with an allele-specific RNA editing (ASED) analysis. We identify 1054 RNA editing events associated with cis genetic polymorphisms. Additionally, we find that a subset of these polymorphisms is linked to genome-wide association study signals of complex traits or diseases. Finally, compared to random cis polymorphisms, polymorphisms associated with RNA editing variation are located closer spatially to their respective editing sites and have a more pronounced impact on RNA secondary structure. Our study reveals widespread cis variation in RNA editing among genetically distinct individuals and sheds light on possible phenotypic consequences of such variation on complex traits and diseases.

Genetic Variation in an Inbred Plant: Variation in Tissue Cultures of Soybean [Glycine Max (L.) Merrill

PubMed Central

Roth, E. J.; Frazier, B. L.; Apuya, N. R.; Lark, K. G.

1989-01-01

Although soybean [Glycine max (L.) Merrill] grows as an inbreeding, generally homozygous, plant, the germplasm of the species contains large amounts of genetic variation. Analysis of soybean DNA has indicated that variation of RFLP (restriction fragment length polymorphism) markers within the species usually entails only two alleles at any one locus and that mixtures of such dimorphic loci account for virtually all of the restriction fragment variation seen in soybean (G. max), and in its ancestors, G. soja and G. gracilis. We report here that tissue cultures prepared from root tissue of individual soybean plants develop RFLP allelic differences at various loci. However, these newly generated alleles are almost always the same as ones previously found and characterized in other varieties of cultivated soybean (cultivars). This repeated generation of particular alleles suggests that much of the genetic variation seen in soybean could be the consequence of specific, relatively frequently employed, recombinational events. Such a mechanism would allow inbred cultivars to generate genetic variation (in the form of alternative alleles) in a controlled manner, perhaps in response to stress. PMID:2567263

Tests of species-specific models reveal the importance of drought in postglacial range shifts of a Mediterranean-climate tree: insights from integrative distributional, demographic and coalescent modelling and ABC model selection.

PubMed

Bemmels, Jordan B; Title, Pascal O; Ortego, Joaquín; Knowles, L Lacey

2016-10-01

Past climate change has caused shifts in species distributions and undoubtedly impacted patterns of genetic variation, but the biological processes mediating responses to climate change, and their genetic signatures, are often poorly understood. We test six species-specific biologically informed hypotheses about such processes in canyon live oak (Quercus chrysolepis) from the California Floristic Province. These hypotheses encompass the potential roles of climatic niche, niche multidimensionality, physiological trade-offs in functional traits, and local-scale factors (microsites and local adaptation within ecoregions) in structuring genetic variation. Specifically, we use ecological niche models (ENMs) to construct temporally dynamic landscapes where the processes invoked by each hypothesis are reflected by differences in local habitat suitabilities. These landscapes are used to simulate expected patterns of genetic variation under each model and evaluate the fit of empirical data from 13 microsatellite loci genotyped in 226 individuals from across the species range. Using approximate Bayesian computation (ABC), we obtain very strong support for two statistically indistinguishable models: a trade-off model in which growth rate and drought tolerance drive habitat suitability and genetic structure, and a model based on the climatic niche estimated from a generic ENM, in which the variables found to make the most important contribution to the ENM have strong conceptual links to drought stress. The two most probable models for explaining the patterns of genetic variation thus share a common component, highlighting the potential importance of seasonal drought in driving historical range shifts in a temperate tree from a Mediterranean climate where summer drought is common. © 2016 John Wiley & Sons Ltd.

Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans

PubMed Central

McDaniell, Ryan; Lee, Bum-Kyu; Song, Lingyun; Liu, Zheng; Boyle, Alan P.; Erdos, Michael R.; Scott, Laura J.; Morken, Mario A.; Kucera, Katerina S.; Battenhouse, Anna; Keefe, Damian; Collins, Francis S.; Willard, Huntington F.; Lieb, Jason D.; Furey, Terrence S.; Crawford, Gregory E.; Iyer, Vishwanath R.; Birney, Ewan

2010-01-01

The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. PMID:20299549

Divergent selection along climatic gradients in a rare central European endemic species, Saxifraga sponhemica

PubMed Central

Walisch, Tania J.; Colling, Guy; Bodenseh, Melanie; Matthies, Diethart

2015-01-01

Background and Aims The effects of habitat fragmentation on quantitative genetic variation in plant populations are still poorly known. Saxifraga sponhemica is a rare endemic of Central Europe with a disjunct distribution, and a stable and specialized habitat of treeless screes and cliffs. This study therefore used S. sponhemica as a model species to compare quantitative and molecular variation in order to explore (1) the relative importance of drift and selection in shaping the distribution of quantitative genetic variation along climatic gradients; (2) the relationship between plant fitness, quantitative genetic variation, molecular genetic variation and population size; and (3) the relationship between the differentiation of a trait among populations and its evolvability. Methods Genetic variation within and among 22 populations from the whole distribution area of S. sponhemica was studied using RAPD (random amplified polymorphic DNA) markers, and climatic variables were obtained for each site. Seeds were collected from each population and germinated, and seedlings were transplanted into a common garden for determination of variation in plant traits. Key Results In contrast to previous results from rare plant species, strong evidence was found for divergent selection. Most population trait means of S. sponhemica were significantly related to climate gradients, indicating adaptation. Quantitative genetic differentiation increased with geographical distance, even when neutral molecular divergence was controlled for, and QST exceeded FST for some traits. The evolvability of traits was negatively correlated with the degree of differentiation among populations (QST), i.e. traits under strong selection showed little genetic variation within populations. The evolutionary potential of a population was not related to its size, the performance of the population or its neutral genetic diversity. However, performance in the common garden was lower for plants from populations with reduced molecular genetic variation, suggesting inbreeding depression due to genetic erosion. Conclusions The findings suggest that studies of molecular and quantitative genetic variation may provide complementary insights important for the conservation of rare species. The strong differentiation of quantitative traits among populations shows that selection can be an important force for structuring variation in evolutionarily important traits even for rare endemic species restricted to very specific habitats. PMID:25862244

Functional implications of Major Histocompatibility (MH) variation using estuarine fish populations.

PubMed

Cohen, Sarah; Tirindelli, Joëlle; Gomez-Chiarri, Marta; Nacci, Diane

2006-12-01

Recently, there has been a dramatic expansion of studies of major histocompatibility complex (MHC) variation aimed at discovering functional differences in immunity across wild populations of diverse vertebrate species. Some species with relatively low genetic diversity or under strong directional selection by pathogens have revealed fascinating cases of MHC allelic disease linkage. More generally in genetically diverse species, however, these linkages may be hard to find. In this paper, we review approaches for assessing functional variation in MHC and discuss their potential use for discovering smaller-scale intraspecific spatial and temporal patterns of MHC variation. Then, we describe and illustrate an approach using the structural model to produce a population composite of variation in antigen-binding regions by mapping population-specific substitutions onto functional regions of the molecule. We are producing models of variation in major histocompatibility (MH) loci for populations of non-migratory fish (killifish, Fundulus heteroclitus) resident at sites that vary dramatically in environmental quality. We discuss the goal of relating MH population variation to functional differences in disease susceptibility such as those inferred by observations of parasitic infection and direct measurement of bacterial challenges in the laboratory. Our study has focused on relatively well-studied killifish populations, including those resident in a highly disturbed, chemically contaminated estuary and nearby less contaminated sites. Population-specific genetic changes at MHC antigen-binding loci are described, and evidence relevant to functional implications of these changes is reviewed. Population-specific patterns of variation in antigen-binding regions in combination with a range of assessments of immune function will provide a powerful new approach to reveal functional changes in MHC.

Yellowstone bison genetics: let us move forward

USGS Publications Warehouse

Halbert, Natalie D.; Gogan, Peter J.P.; Hedrick, Philip W.; Wahl, Jacquelyn M.; Derr, James N.

2012-01-01

White and Wallen (2012) disagree with the conclusions and suggestions made in our recent assessment of population structure among Yellowstone National Park (YNP) bison based on 46 autosomal microsatellite loci in 661 animals (Halbert et al. 2012). First, they suggest that "the existing genetic substructure (that we observed) was artificially created." Specifically, they suggest that the substructure observed between the northern and central populations is the result of human activities, both historical and recent. In fact, the genetic composition of all known existing bison herds was created by, or has been influenced by, anthropogenic activities, although this obviously does not reduce the value of these herds for genetic conservation (Dratch and Gogan 2010). As perspective, many, if not most, species of conservation concern have been influenced by human actions and as a result currently exist as isolated populations. However, it is quite difficult to distinguish between genetic differences caused by human actions and important ancestral variation contained in separate populations without data from early time periods. Therefore, to not lose genetic variation that may be significant or indicative of important genetic variation, the generally acceptable management approach is to attempt to retain this variation based on the observed population genetic subdivision (Hedrick et al. 1986).

Genetic sex determination and extinction.

PubMed

Hedrick, Philip W; Gadau, Jürgen; Page, Robert E

2006-02-01

Genetic factors can affect the probability of extinction either by increasing the effect of detrimental variants or by decreasing the potential for future adaptive responses. In a recent paper, Zayed and Packer demonstrate that low variation at a specific locus, the complementary sex determination (csd) locus in Hymenoptera (ants, bees and wasps), can result in a sharply increased probability of extinction. Their findings illustrate situations in which there is a feedback process between decreased genetic variation at the csd locus owing to genetic drift and decreased population growth, resulting in an extreme type of extinction vortex for these ecologically important organisms.

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

PubMed Central

Poon, Art F. Y; Kosakovsky Pond, Sergei L.; Bennett, Phil; Richman, Douglas D; Leigh Brown, Andrew J.; Frost, Simon D. W

2007-01-01

CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design. PMID:17397261

Genetic variation in Toll-like receptors and disease susceptibility.

PubMed

Netea, Mihai G; Wijmenga, Cisca; O'Neill, Luke A J

2012-05-18

Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such as MyD88-IRAK4 or TLR3-Unc93b-TRIF-TRAF3, have demonstrated the specific roles of these pathways in host defense against pyogenic bacteria and herpesviruses, respectively. Second, common polymorphisms in genes encoding several TLRs and associated genes have been associated with both infectious and autoimmune diseases. The study of genetic variation in TLRs in various populations combined with information on infection has demonstrated complex interaction between genetic variation in TLRs and environmental factors. This interaction explains the differences in the effect of TLR polymorphisms on susceptibility to infection and autoimmune disease in various populations.

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans

PubMed Central

Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W.; Grubert, Fabian; Candille, Sophie I.; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L.; Tang, Hua; Ricci, Emiliano; Snyder, Michael P.

2015-01-01

Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy—many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. PMID:26297486

Genetic Determinants of Pubertal Timing in the General Population

PubMed Central

Gajdos, Zofia K.Z.; Henderson, Katherine D.; Hirschhorn, Joel N.

2010-01-01

Puberty is an important developmental stage during which reproductive capacity is attained. The timing of puberty varies greatly among healthy individuals in the general population and is influenced by both genetic and environmental factors. Although genetic variation is known to influence the normal spectrum of pubertal timing, the specific genes involved remain largely unknown. Genetic analyses have identified a number of genes responsible for rare disorders of pubertal timing such as hypogonadotropic hypogonadism and Kallmann syndrome. Recently, the first loci with common variation reproducibly associated with population variation in the timing of puberty were identified at 6q21 in or near LIN28B and at 9q31.2. However, these two loci explain only a small fraction of the genetic contribution to population variation in pubertal timing, suggesting the need to continue to consider other loci and other types of variants. Here we provide an update of the genes implicated in disorders of puberty, discuss genes and pathways that may be involved in the timing of normal puberty, and suggest additional avenues of investigation to identify genetic regulators of puberty in the general population. PMID:20144687

GlobAl Distribution of GEnetic Traits (GADGET) web server: polygenic trait scores worldwide.

PubMed

Chande, Aroon T; Wang, Lu; Rishishwar, Lavanya; Conley, Andrew B; Norris, Emily T; Valderrama-Aguirre, Augusto; Jordan, I King

2018-05-18

Human populations from around the world show striking phenotypic variation across a wide variety of traits. Genome-wide association studies (GWAS) are used to uncover genetic variants that influence the expression of heritable human traits; accordingly, population-specific distributions of GWAS-implicated variants may shed light on the genetic basis of human phenotypic diversity. With this in mind, we developed the GlobAl Distribution of GEnetic Traits web server (GADGET http://gadget.biosci.gatech.edu). The GADGET web server provides users with a dynamic visual platform for exploring the relationship between worldwide genetic diversity and the genetic architecture underlying numerous human phenotypes. GADGET integrates trait-implicated single nucleotide polymorphisms (SNPs) from GWAS, with population genetic data from the 1000 Genomes Project, to calculate genome-wide polygenic trait scores (PTS) for 818 phenotypes in 2504 individual genomes. Population-specific distributions of PTS are shown for 26 human populations across 5 continental population groups, with traits ordered based on the extent of variation observed among populations. Users of GADGET can also upload custom trait SNP sets to visualize global PTS distributions for their own traits of interest.

Host genetic variation influences gene expression response to rhinovirus infection.

PubMed

Çalışkan, Minal; Baker, Samuel W; Gilad, Yoav; Ober, Carole

2015-04-01

Rhinovirus (RV) is the most prevalent human respiratory virus and is responsible for at least half of all common colds. RV infections may result in a broad spectrum of effects that range from asymptomatic infections to severe lower respiratory illnesses. The basis for inter-individual variation in the response to RV infection is not well understood. In this study, we explored whether host genetic variation is associated with variation in gene expression response to RV infections between individuals. To do so, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We mapped local and distant genetic variation that is associated with inter-individual differences in gene expression levels (eQTLs) in both uninfected and RV-infected cells. We focused specifically on response eQTLs (reQTLs), namely, genetic associations with inter-individual variation in gene expression response to RV infection. We identified local reQTLs for 38 genes, including genes with known functions in viral response (UBA7, OAS1, IRF5) and genes that have been associated with immune and RV-related diseases (e.g., ITGA2, MSR1, GSTM3). The putative regulatory regions of genes with reQTLs were enriched for binding sites of virus-activated STAT2, highlighting the role of condition-specific transcription factors in genotype-by-environment interactions. Overall, we suggest that the 38 loci associated with inter-individual variation in gene expression response to RV-infection represent promising candidates for affecting immune and RV-related respiratory diseases.

Genetic determinants of prepubertal and pubertal growth and development.

PubMed

Thomis, Martine A; Towne, Bradford

2006-12-01

This article surveys the current general understanding of genetic influences on within- and between-population variation in growth and development in the context of establishing an International Growth Standard for Preadolescent and Adolescent Children. Traditional genetic epidemiologic analysis methods are reviewed, and evidence from family studies for genetic effects on different measures of growth and development is then presented. Findings from linkage and association studies seeking to identify specific genomic locations and allelic variants of genes influencing variation in growth and maturation are then summarized. Special mention is made of the need to study the interactions between genes and environments. At present, specific genes and polymorphisms contributing to variation in growth and maturation are only beginning to be identified. Larger genetic epidemiologic studies are needed in different parts of the world to better explore population differences in gene frequencies and gene-environment interactions. As advances continue to be made in molecular and statistical genetic methods, the genetic architecture of complex processes, including those of growth and development, will become better elucidated. For now, it can only be concluded that although the fundamental genetic underpinnings of the growth and development of children worldwide are likely to be essentially the same, there are also likely to be differences between populations in the frequencies of allelic gene variants that influence growth and maturation and in the nature of gene-environment interactions. This does not necessarily preclude an international growth reference, but it does have important implications for the form that such a reference might ultimately take.

Genetic variations of the SLCO1B1 gene in the Chinese, Malay and Indian populations of Singapore.

PubMed

Ho, Woon Fei; Koo, Seok Hwee; Yee, Jie Yin; Lee, Edmund Jon Deoon

2008-01-01

OATP1B1 is a liver-specific transporter that mediates the uptake of various endogenous and exogenous compounds including many clinically used drugs from blood into hepatocytes. This study aims to identify genetic variations of SLCO1B1 gene in three distinct ethnic groups of the Singaporean population (n=288). The coding region of the gene encoding the transporter protein was screened for genetic variations in the study population by denaturing high-performance liquid chromatography and DNA sequencing. Twenty-five genetic variations of SLCO1B1, including 10 novel ones, were found: 13 in the coding exons (9 nonsynonymous and 4 synonymous variations), 6 in the introns, and 6 in the 3' untranslated region. Four novel nonsynonymous variations: 633A>G (Ile211Met), 875C>T (Ala292Val), 1837T>C (Cys613Arg), and 1877T>A (Leu626Stop) were detected as heterozygotes. Among the novel nonsynonymous variations, 633A>G, 1837T>C, and 1877T>A were predicted to be functionally significant. These data would provide fundamental and useful information for pharmacogenetic studies on drugs that are substrates of OATP1B1 in Asians.

A Drosophila model for toxicogenomics: Genetic variation in susceptibility to heavy metal exposure

PubMed Central

Luoma, Sarah E.; St. Armour, Genevieve E.; Thakkar, Esha

2017-01-01

The genetic factors that give rise to variation in susceptibility to environmental toxins remain largely unexplored. Studies on genetic variation in susceptibility to environmental toxins are challenging in human populations, due to the variety of clinical symptoms and difficulty in determining which symptoms causally result from toxic exposure; uncontrolled environments, often with exposure to multiple toxicants; and difficulty in relating phenotypic effect size to toxic dose, especially when symptoms become manifest with a substantial time lag. Drosophila melanogaster is a powerful model that enables genome-wide studies for the identification of allelic variants that contribute to variation in susceptibility to environmental toxins, since the genetic background, environmental rearing conditions and toxic exposure can be precisely controlled. Here, we used extreme QTL mapping in an outbred population derived from the D. melanogaster Genetic Reference Panel to identify alleles associated with resistance to lead and/or cadmium, two ubiquitous environmental toxins that present serious health risks. We identified single nucleotide polymorphisms (SNPs) associated with variation in resistance to both heavy metals as well as SNPs associated with resistance specific to each of them. The effects of these SNPs were largely sex-specific. We applied mutational and RNAi analyses to 33 candidate genes and functionally validated 28 of them. We constructed networks of candidate genes as blueprints for orthologous networks of human genes. The latter not only provided functional contexts for known human targets of heavy metal toxicity, but also implicated novel candidate susceptibility genes. These studies validate Drosophila as a translational toxicogenomics gene discovery system. PMID:28732062

Maintenance of genetic variation in sexual ornaments: a review of the mechanisms.

PubMed

Radwan, Jacek

2008-09-01

Female preferences for elaborate male sexual traits have been documented in a number of species in which males contribute only genes to the next generation. In such systems, mate choice has been hypothesised to benefit females genetically. For the genetic benefits to be possible there must be additive genetic variation (V A) for sexual ornaments, such that highly ornamented males can pass fitter genes on to the progeny of choosy females. Here, I review the mechanisms that can contribute to the maintenance of this variation. The variation may be limited to sexual ornaments, resulting in Fisherian benefits in terms of the increased reproductive success of male progeny produced by choosy females. Alternatively, ornaments may capture V A in other life-history traits. In the latter case, "good genes" benefits may apply in terms of improved performance of the progeny of either sex. Some mechanisms, however, such as negative pleiotropy, sexually antagonistic variation or overdominance, can maintain V A in ornaments and other life-history traits with little variation in total fitness, leaving little room for any genetic benefits of mate choice. Distinguishing between these mechanisms has consequences not only for the theory of sexual selection, but also for evolution of sex and for biological conservation. I discuss how the traditional ways of testing for genetic benefits can usefully be supplemented by tests detecting benefits resulting from specific mechanisms maintaining V A in sexual ornaments.

Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism

PubMed Central

Reilly, Matthew T.; Harris, R. Adron; Noronha, Antonio

2012-01-01

Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene’s function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput “next-generation sequencing” technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism. PMID:23134044

Using genetically engineered animal models in the postgenomic era to understand gene function in alcoholism.

PubMed

Reilly, Matthew T; Harris, R Adron; Noronha, Antonio

2012-01-01

Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene's function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput "next-generation sequencing" technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism.

Phylogeny and assemblage composition of Frankia in Alnus tenuifolia nodules across a primary successional sere in interior Alaska

Treesearch

M.D. Anderson; D.L. Taylor; R.W. Ruess

2013-01-01

In nitrogen (N) fixing symbioses, host-symbiont specificity, genetic variation in bacterial symbionts and environmental variation represent fundamental constraints on the ecology, evolution and practical uses of these interactions, but detailed information is lacking for many naturally occurring N-fixers. This study examined phylogenetic host specificity of ...

Phenotypic Variation in Specific Gravity and Fiber Length of Cherrybark Oak

Treesearch

R. E. Farmer

1969-01-01

Knowledge of variation in oakwood properties that are related to pulp yield and quality is essential in genetic improvement research. Two important properties that can be studied easily are specific gravity and fiber length. This paper reports a study made to develop a guide to field selection of breeding material in cherrybark oak (Quercus falcala...

Genomic data reveal a loss of diversity in two species of tuco-tucos (genus Ctenomys) following a volcanic eruption.

PubMed

Hsu, Jeremy L; Crawford, Jeremy Chase; Tammone, Mauro N; Ramakrishnan, Uma; Lacey, Eileen A; Hadly, Elizabeth A

2017-11-24

Marked reductions in population size can trigger corresponding declines in genetic variation. Understanding the precise genetic consequences of such reductions, however, is often challenging due to the absence of robust pre- and post-reduction datasets. Here, we use heterochronous genomic data from samples obtained before and immediately after the 2011 eruption of the Puyehue-Cordón Caulle volcanic complex in Patagonia to explore the genetic impacts of this event on two parapatric species of rodents, the colonial tuco-tuco (Ctenomys sociabilis) and the Patagonian tuco-tuco (C. haigi). Previous analyses using microsatellites revealed no post-eruption changes in genetic variation in C. haigi, but an unexpected increase in variation in C. sociabilis. To explore this outcome further, we used targeted gene capture to sequence over 2,000 putatively neutral regions for both species. Our data revealed that, contrary to the microsatellite analyses, the eruption was associated with a small but significant decrease in genetic variation in both species. We suggest that genome-level analyses provide greater power than traditional molecular markers to detect the genetic consequences of population size changes, particularly changes that are recent, short-term, or modest in size. Consequently, genomic analyses promise to generate important new insights into the effects of specific environmental events on demography and genetic variation.

ETHNOS: A versatile electronic tool for the development and curation of national genetic databases

PubMed Central

2010-01-01

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available software which runs more than half of the NEMDBs currently available. Given the emerging need for NEMDB in genetic testing services and the fact that ETHNOS is the only off-the-shelf software available for NEMDB development and curation, its adoption in subsequent NEMDB development would contribute towards data content uniformity, unlike the diverse contents and quality of the available gene (locus)-specific databases. Finally, we allude to the potential applications of NEMDBs, not only as worldwide central allele frequency repositories, but also, and most importantly, as data warehouses of individual-level genomic data, hence allowing for a comprehensive ethnicity-specific documentation of genomic variation. PMID:20650823

ETHNOS : A versatile electronic tool for the development and curation of national genetic databases.

PubMed

van Baal, Sjozef; Zlotogora, Joël; Lagoumintzis, George; Gkantouna, Vassiliki; Tzimas, Ioannis; Poulas, Konstantinos; Tsakalidis, Athanassios; Romeo, Giovanni; Patrinos, George P

2010-06-01

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available software which runs more than half of the NEMDBs currently available. Given the emerging need for NEMDB in genetic testing services and the fact that ETHNOS is the only off-the-shelf software available for NEMDB development and curation, its adoption in subsequent NEMDB development would contribute towards data content uniformity, unlike the diverse contents and quality of the available gene (locus)-specific databases. Finally, we allude to the potential applications of NEMDBs, not only as worldwide central allele frequency repositories, but also, and most importantly, as data warehouses of individual-level genomic data, hence allowing for a comprehensive ethnicity-specific documentation of genomic variation.

A matching-allele model explains host resistance to parasites.

PubMed

Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

2013-06-17

The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

Genetic Variation within a Lotic Population of Janthinobacterium lividum

PubMed Central

Saeger, Jennifer L.; Hale, Alan B.

1993-01-01

An understanding of the genetic variation within and between populations should allow scientists to address many problems, including those associated with endangered species and the release of genetically modified organisms into the environment. With respect to microorganisms, the release of genetically engineered microorganisms is likely to increase dramatically given the current growth in the bioremediation industry. In this study, genetic variation within a lotic, bacterial population of Janthinobacterium lividum was measured with restriction fragment length polymorphism analysis. Chromosomal DNA from 10 Kettle Creek (Hawk Mountain Sanctuary, Kempton, Pa.) J. lividum isolates was digested with six restriction endonucleases and probed with a 7.5-kb pKK3535 fragment containing the E. coli rrnB rRNA operon. Genetic variation, as measured in terms of nucleotide diversity, was high within the population. The 0.0781 value for genetic variation was especially high given the conservative nature of the genetic probe. The average percent similarity among isolates within the population was 67.25%. Pairwise comparisons of nucleotide diversity values (π) and similarity coefficients (F) yielded values ranging from 0.0032 to 0.1816 and 0.3363 to 0.9808, respectively. Putative clonemates were not present within the group of isolates; however, all isolates shared 14 fragments across a spectrum of six restriction enzymes. The presence of these common fragments indicates that restriction fragment length polymorphism analysis may provide population- or species-specific diagnostic markers for J. lividum. Data that suggest a plume effect with respect to the downstream movement of J. lividum are also presented. An increase in genetic variation within groups of isolates along the longitudinal gradient of Kettle Creek is also suggested. PMID:16348995

Genetic Variation within a Lotic Population of Janthinobacterium lividum.

PubMed

Saeger, J L; Hale, A B

1993-07-01

An understanding of the genetic variation within and between populations should allow scientists to address many problems, including those associated with endangered species and the release of genetically modified organisms into the environment. With respect to microorganisms, the release of genetically engineered microorganisms is likely to increase dramatically given the current growth in the bioremediation industry. In this study, genetic variation within a lotic, bacterial population of Janthinobacterium lividum was measured with restriction fragment length polymorphism analysis. Chromosomal DNA from 10 Kettle Creek (Hawk Mountain Sanctuary, Kempton, Pa.) J. lividum isolates was digested with six restriction endonucleases and probed with a 7.5-kb pKK3535 fragment containing the E. coli rrnB rRNA operon. Genetic variation, as measured in terms of nucleotide diversity, was high within the population. The 0.0781 value for genetic variation was especially high given the conservative nature of the genetic probe. The average percent similarity among isolates within the population was 67.25%. Pairwise comparisons of nucleotide diversity values (pi) and similarity coefficients (F) yielded values ranging from 0.0032 to 0.1816 and 0.3363 to 0.9808, respectively. Putative clonemates were not present within the group of isolates; however, all isolates shared 14 fragments across a spectrum of six restriction enzymes. The presence of these common fragments indicates that restriction fragment length polymorphism analysis may provide population- or species-specific diagnostic markers for J. lividum. Data that suggest a plume effect with respect to the downstream movement of J. lividum are also presented. An increase in genetic variation within groups of isolates along the longitudinal gradient of Kettle Creek is also suggested.

Sequence-length variation of mtDNA HVS-I C-stretch in Chinese ethnic groups.

PubMed

Chen, Feng; Dang, Yong-hui; Yan, Chun-xia; Liu, Yan-ling; Deng, Ya-jun; Fulton, David J R; Chen, Teng

2009-10-01

The purpose of this study was to investigate mitochondrial DNA (mtDNA) hypervariable segment-I (HVS-I) C-stretch variations and explore the significance of these variations in forensic and population genetics studies. The C-stretch sequence variation was studied in 919 unrelated individuals from 8 Chinese ethnic groups using both direct and clone sequencing approaches. Thirty eight C-stretch haplotypes were identified, and some novel and population specific haplotypes were also detected. The C-stretch genetic diversity (GD) values were relatively high, and probability (P) values were low. Additionally, C-stretch length heteroplasmy was observed in approximately 9% of individuals studied. There was a significant correlation (r=-0.961, P<0.01) between the expansion of the cytosine sequence length in the C-stretch of HVS-I and a reduction in the number of upstream adenines. These results indicate that the C-stretch could be a useful genetic maker in forensic identification of Chinese populations. The results from the Fst and dA genetic distance matrix, neighbor-joining tree, and principal component map also suggest that C-stretch could be used as a reliable genetic marker in population genetics.

Genetics and the physiological ecology of conifers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitton, J.B.

1995-07-01

Natural selection acts on the diversity of genotypes, adapting populations to their specific environments and driving evolution in response to changes in climate. Genetically based differences in physiology and demography adapt species to alternate environments and produce, along with historical accidents, the present distribution of species. The sorting of conifer species by elevation is so marked that conifers help to define plant communities arranged in elevational bands in the Rocky Mountains. For these reasons, a genetic perspective is necessary to appreciate the evolution of ecophysiological patterns in the coniferous forests of the Rocky Mountains. The fascinating natural history and themore » economic importance of western conifers have stimulated numerous studies of their ecology, ecological genetics, and geographic variation. These studies yield some generalizations, and present some puzzling contradictions. This chapter focuses on the genetic variability associated with the physiological differences among genotypes in Rocky Mountain conifers. Variation among genotypes in survival, growth, and resistance to herbivores is used to illustrate genetically based differences in physiology, and to suggest the mechanistic studies needed to understand the relationships between genetic and physiological variation.« less

Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.

PubMed

Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W; Grubert, Fabian; Candille, Sophie I; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L; Tang, Hua; Ricci, Emiliano; Snyder, Michael P

2015-11-01

Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy--many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. © 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.

Genotype-by-environment interactions leads to variable selection on life-history strategy in Common Evening Primrose (Oenothera biennis).

PubMed

Johnson, M T J

2007-01-01

Monocarpic plant species, where reproduction is fatal, frequently exhibit variation in the length of their prereproductive period prior to flowering. If this life-history variation in flowering strategy has a genetic basis, genotype-by-environment interactions (G x E) may maintain phenotypic diversity in flowering strategy. The native monocarpic plant Common Evening Primrose (Oenothera biennis L., Onagraceae) exhibits phenotypic variation for annual vs. biennial flowering strategies. I tested whether there was a genetic basis to variation in flowering strategy in O. biennis, and whether environmental variation causes G x E that imposes variable selection on flowering strategy. In a field experiment, I randomized more than 900 plants from 14 clonal families (genotypes) into five distinct habitats that represented a natural productivity gradient. G x E strongly affected the lifetime fruit production of O. biennis, with the rank-order in relative fitness of genotypes changing substantially between habitats. I detected genetic variation in annual vs. biennial strategies in most habitats, as well as a G x E effect on flowering strategy. This variation in flowering strategy was correlated with genetic variation in relative fitness, and phenotypic and genotypic selection analyses revealed that environmental variation resulted in variable directional selection on annual vs. biennial strategies. Specifically, a biennial strategy was favoured in moderately productive environments, whereas an annual strategy was favoured in low-productivity environments. These results highlight the importance of variable selection for the maintenance of genetic variation in the life-history strategy of a monocarpic plant.

Natural variation in germination responses of Arabidopsis to seasonal cues and their associated physiological mechanisms

PubMed Central

Barua, Deepak; Butler, Colleen; Tisdale, Tracy E.; Donohue, Kathleen

2012-01-01

Background and Aims Despite the intense interest in phenological adaptation to environmental change, the fundamental character of natural variation in germination is almost entirely unknown. Specifically, it is not known whether different genotypes within a species are germination specialists to particular conditions, nor is it known what physiological mechanisms of germination regulation vary in natural populations and how they are associated with responses to particular environmental factors. Methods We used a set of recombinant inbred genotypes of Arabidopsis thaliana, in which linkage disequilibrium has been disrupted over seven generations, to test for genetic variation and covariation in germination responses to distinct environmental factors. We then examined physiological mechanisms associated with those responses, including seed-coat permeability and sensitivity to the phytohormones gibberellic acid (GA) and abscisic acid (ABA). Key Results Genetic variation for germination was environment-dependent, but no evidence for specialization of germination to different conditions was found. Hormonal sensitivities also exhibited significant genetic variation, but seed-coat properties did not. GA sensitivity was associated with germination responses to multiple environmental factors, but seed-coat permeability and ABA sensitivity were associated with specific germination responses, suggesting that an evolutionary change in GA sensitivity could affect germination in multiple environments, but that of ABA sensitivity may affect germination under more restricted conditions. Conclusions The physiological mechanisms of germination responses to specific environmental factors therefore can influence the ability to adapt to diverse seasonal environments encountered during colonization of new habitats or with future predicted climate change. PMID:22012958

Seed source variation in tracheid length and specific gravity of five-year-old jack pine seedlings

Treesearch

James P. King

1968-01-01

Jack pine (Pinus banksiana Lamb.) is widely used in Lake States reforestation because of its ability to make rapid early growth on relatively infertile sites. It is a major pulpwood producing species. Since the quality and yield of pulp are so strongly influenced by tracheid length and specific gravity, information on genetic variation in these...

Genetic variation in the microfibril angle of loblolly pine from two test sites

Treesearch

Jennifer H. Myszewski; Floyd E. Bridgwater; William J. Lowe; Thomas D. Byram; Robert A. Megraw

2004-01-01

In recent years, several studies have examined the effect of microfibril angle (MFA) on wood quality. However, little research has been conducted upon the genetic mechanisms controlling MFA. In this study, we examined the heritability of MFA in loblolly pine, Pinus taeda L., and its genetic relationships with height, diameter, volume, and specific...

Harmonizing the interpretation of genetic variants across the world: the Malaysian experience.

PubMed

Hassan, Nik Norliza Nik; Plazzer, John-Paul; Smith, Timothy D; Halim-Fikri, Hashim; Macrae, Finlay; Zubaidi, A A L; Zilfalil, Bin Alwi

2016-02-26

Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations. The ethical, legal, social issues, intellectual property, ownership of the data, information technology implementation, and efforts to improve the standards and systems used in data sharing are discussed. An overarching framework such as provided by the Human Variome Project to co-ordinate activities is invaluable. Country Nodes, such as MyHVP, enable human gene variation associated with human diseases to be collected, stored and shared by all disciplines (clinicians, molecular biologists, pathologists, bioinformaticians) for a consistent interpretation of genetic variants locally and across the world.

Recent advances in the molecular genetics of epilepsy.

PubMed

Hildebrand, Michael S; Dahl, Hans-Henrik M; Damiano, John Anthony; Smith, Richard J H; Scheffer, Ingrid E; Berkovic, Samuel F

2013-05-01

Recent advances in molecular genetics have translated into the increasing utilisation of genetic testing in the routine clinical practice of neurologists. There has been a steady, incremental increase in understanding the genetic variation associated with epilepsies. Genetic testing in the epilepsies is not yet widely practiced, but the advent of new screening technologies promises to exponentially expand both knowledge and clinical utility. To maximise the value of this new genetic insight we need to rapidly extrapolate genetic findings to inform patients of their diagnosis, prognosis, recurrence risk and the clinical management options available for their specific genetic condition. Comprehensive, highly specific and sensitive genetic test results improve the management of patients by neurologists and clinical geneticists. Here we discuss the latest developments in clinical genetic testing for epilepsy and describe new molecular genetics platforms that will transform both genetic screening and novel gene discovery.

Origin of genetic variation: regulation of genetic recombination in the higher organisms - a theory.

PubMed

Pandey, K K

1972-01-01

Recent studies in the fungi, particularly Neurospora and Schizophyllum, have revealed a number of genetic features which, viewed in conjunction with earlier observations on other organisms, form a pattern, or model, which appears to be basic to the control of recombination in all eukaryotes, including higher organisms. It is assumed that the control is exercised on mechanisms that produce new alleles through recombination, as understood in broad terms and including such a likely phenomenon as gene conversion, which may or may not involve crossing-over, as well as equal and unequal crossing-over. The recombination may thus occur between alleles in either the homozygous or heterozygous condition. In the model, regulatory genes and breeding behaviour are integrated into one self-regulatory system controlling the production of new genetic variation.The model is based on the following five general features, largely substantiated by the results in Neurospora and Schizophyllum: 1) The frequency of recombination in a particular chromosomal region is controlled by specific regulatory genes (rec). 2) There may be a number of such specific, regulatory genes responsible for recombination in a given region. 3) A rec. locus may influence recombination in more than one region. 4) The regulatory genes have no specific physical relationship with the region(s) they control, and are usually located at random in the genome. 5) Of the allelic forms of the regulatory genes it is always the dominant gene which suppresses recombination and the recessive gene which increases recombination. The rec system is epistatic to other genetic elements jointly involved in the overall control of recombination in a specific region. It is suggested that usually the control of recombination in a given region is exercised, cumulatively, by the balance of the dominant and recessive genes of the specific rec loci in the organism. Outbreeding, with the associated high heterozygosity of the regulatory rec loci, virtually "switches off" recombination, producing few new variations. Inbreeding produces homozygosity of these loci, resulting in certain individuals which will have a considerable number of their regulatory loci in the homozygous recessive condition and in which recombination will be "switched on", producing new variation at a high frequency. Inbreeding is thus an integrated, evolutionary system of considerable importance, and is not a degenerate "dead end", as many investigators have previously thought.The model has another compensatory function in evolution. In major loci, or in an operon, where there are structural genes and closely linked operator genes, as exemplified by the S locus, there are indications that the present model is concerned with the regulation of both structural and operator genes. The consequences of the model in the two classes of genes, however, are in direct contrast to each other: High heterozygosity which is instrumental in switching "off" recombination, and which is therefore helpful in maintaining stability in the structural gene, is conducive to functional variation of the operator gene; and high homozygosity, which is instrumental in switching "on" recombination, and which is therefore helpful in producing variation in the structural gene, is conducive to the stability of the operator gene.This model of the control of genetic variation in a specific chromosomal region is significant in development as well as in evolution, and throws light on a number of hitherto "intractable" problems peculiar to the higher organisms. For example, the model is helpful in explaining: 1) the origin of new self-incompatibility alleles in the flowering plants; 2) the impressive speciation in the waif flora (and fauna) of the oceanic islands; 3) the presence of high genetic variability in inbreeding species of plants; 4) environmentally-induced heritable variation in certain plants; and 5) the genetic mechanism of antibody diversity in animals.

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.

PubMed

Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B

2017-11-24

Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.

Genetically based population divergence in overwintering energy mobilization in brook charr (Salvelinus fontinalis).

PubMed

Crespel, Amélie; Bernatchez, Louis; Garant, Dany; Audet, Céline

2013-03-01

Investigating the nature of physiological traits potentially related to fitness is important towards a better understanding of how species and/or populations may respond to selective pressures imposed by contrasting environments. In northern species in particular, the ability to mobilize energy reserves to compensate for the low external energy intake during winter is crucial. However, the phenotypic and genetic bases of energy reserve accumulation and mobilization have rarely been investigated, especially pertaining to variation in strategy adopted by different populations. In the present study, we documented variation in several energy reserve variables and estimated their quantitative genetic basis to test the null hypothesis of no difference in variation at those traits among three strains of brook charr (Salvelinus fontinalis) and their reciprocal hybrids. Our results indicate that the strategy of winter energy preparation and mobilization was specific to each strain, whereby (1) domestic fish accumulated a higher amount of energy reserves before winter and kept accumulating liver glycogen during winter despite lower feeding; (2) Laval fish used liver glycogen and lipids during winter and experienced a significant decrease in condition factor; (3) Rupert fish had relatively little energy reserves accumulated at the end of fall and preferentially mobilized visceral fat during winter. Significant heritability for traits related to the accumulation and use of energy reserves was found in the domestic and Laval but not in the Rupert strain. Genetic and phenotypic correlations also varied among strains, which suggested population-specific genetic architecture underlying the expression of these traits. Hybrids showed limited evidence of non-additive effects. Overall, this study provides the first evidence of a genetically based-and likely adaptive-population-specific strategy for energy mobilization related to overwinter survival.

The study of human Y chromosome variation through ancient DNA.

PubMed

Kivisild, Toomas

2017-05-01

High throughput sequencing methods have completely transformed the study of human Y chromosome variation by offering a genome-scale view on genetic variation retrieved from ancient human remains in context of a growing number of high coverage whole Y chromosome sequence data from living populations from across the world. The ancient Y chromosome sequences are providing us the first exciting glimpses into the past variation of male-specific compartment of the genome and the opportunity to evaluate models based on previously made inferences from patterns of genetic variation in living populations. Analyses of the ancient Y chromosome sequences are challenging not only because of issues generally related to ancient DNA work, such as DNA damage-induced mutations and low content of endogenous DNA in most human remains, but also because of specific properties of the Y chromosome, such as its highly repetitive nature and high homology with the X chromosome. Shotgun sequencing of uniquely mapping regions of the Y chromosomes to sufficiently high coverage is still challenging and costly in poorly preserved samples. To increase the coverage of specific target SNPs capture-based methods have been developed and used in recent years to generate Y chromosome sequence data from hundreds of prehistoric skeletal remains. Besides the prospects of testing directly as how much genetic change in a given time period has accompanied changes in material culture the sequencing of ancient Y chromosomes allows us also to better understand the rate at which mutations accumulate and get fixed over time. This review considers genome-scale evidence on ancient Y chromosome diversity that has recently started to accumulate in geographic areas favourable to DNA preservation. More specifically the review focuses on examples of regional continuity and change of the Y chromosome haplogroups in North Eurasia and in the New World.

The epigenomic landscape of African rainforest hunter-gatherers and farmers.

PubMed

Fagny, Maud; Patin, Etienne; MacIsaac, Julia L; Rotival, Maxime; Flutre, Timothée; Jones, Meaghan J; Siddle, Katherine J; Quach, Hélène; Harmant, Christine; McEwen, Lisa M; Froment, Alain; Heyer, Evelyne; Gessain, Antoine; Betsem, Edouard; Mouguiama-Daouda, Patrick; Hombert, Jean-Marie; Perry, George H; Barreiro, Luis B; Kobor, Michael S; Quintana-Murci, Lluis

2015-11-30

The genetic history of African populations is increasingly well documented, yet their patterns of epigenomic variation remain uncharacterized. Moreover, the relative impacts of DNA sequence variation and temporal changes in lifestyle and habitat on the human epigenome remain unknown. Here we generate genome-wide genotype and DNA methylation profiles for 362 rainforest hunter-gatherers and sedentary farmers. We find that the current habitat and historical lifestyle of a population have similarly critical impacts on the methylome, but the biological functions affected strongly differ. Specifically, methylation variation associated with recent changes in habitat mostly concerns immune and cellular functions, whereas that associated with historical lifestyle affects developmental processes. Furthermore, methylation variation--particularly that correlated with historical lifestyle--shows strong associations with nearby genetic variants that, moreover, are enriched in signals of natural selection. Our work provides new insight into the genetic and environmental factors affecting the epigenomic landscape of human populations over time.

Does the central dogma still stand?

PubMed

Koonin, Eugene V

2012-08-23

Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general 'look-ahead effect' of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits.

Genetic Dissection of Anopheles gambiae Gut Epithelial Responses to Serratia marcescens

PubMed Central

Stathopoulos, Stavros; Neafsey, Daniel E.; Lawniczak, Mara K. N.; Muskavitch, Marc A. T.; Christophides, George K.

2014-01-01

Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component. PMID:24603764

Combining quantitative trait loci analysis with physiological models to predict genotype-specific transpiration rates.

PubMed

Reuning, Gretchen A; Bauerle, William L; Mullen, Jack L; McKay, John K

2015-04-01

Transpiration is controlled by evaporative demand and stomatal conductance (gs ), and there can be substantial genetic variation in gs . A key parameter in empirical models of transpiration is minimum stomatal conductance (g0 ), a trait that can be measured and has a large effect on gs and transpiration. In Arabidopsis thaliana, g0 exhibits both environmental and genetic variation, and quantitative trait loci (QTL) have been mapped. We used this information to create a genetically parameterized empirical model to predict transpiration of genotypes. For the parental lines, this worked well. However, in a recombinant inbred population, the predictions proved less accurate. When based only upon their genotype at a single g0 QTL, genotypes were less distinct than our model predicted. Follow-up experiments indicated that both genotype by environment interaction and a polygenic inheritance complicate the application of genetic effects into physiological models. The use of ecophysiological or 'crop' models for predicting transpiration of novel genetic lines will benefit from incorporating further knowledge of the genetic control and degree of independence of core traits/parameters underlying gs variation. © 2014 John Wiley & Sons Ltd.

Comparison of the effectiveness of ISJ and SSR markers and detection of outlier loci in conservation genetics of Pulsatilla patens populations

PubMed Central

Szczecińska, Monika

2016-01-01

Background Research into the protection of rare and endangered plant species involves genetic analyses to determine their genetic variation and genetic structure. Various categories of genetic markers are used for this purpose. Microsatellites, also known as simple sequence repeats (SSR), are the most popular category of markers in population genetics research. In most cases, microsatellites account for a large part of the noncoding DNA and exert a neutral effect on the genome. Neutrality is a desirable feature in evaluations of genetic differences between populations, but it does not support analyses of a population’s ability to adapt to a given environment or its evolutionary potential. Despite the numerous advantages of microsatellites, non-neutral markers may supply important information in conservation genetics research. They are used to evaluate adaptation to specific environmental conditions and a population’s adaptive potential. The aim of this study was to compare the level of genetic variation in Pulsatilla patens populations revealed by neutral SSR markers and putatively adaptive ISJ markers (intron-exon splice junction). Methods The experiment was conducted on 14 Polish populations of P. patens and three P. patens populations from the nearby region of Vitebsk in Belarus. A total of 345 individuals were examined. Analyses were performed with the use of eight SSR primers specific to P. patens and three ISJ primers. Results SSR markers revealed a higher level of genetic variation than ISJ markers (He = 0.609, He = 0.145, respectively). An analysis of molecular variance (AMOVA) revealed that, the overall genetic diversity between the analyzed populations defined by parameters FST and ΦPT for SSR (20%) and ΦPT for ISJ (21%) markers was similar. Analysis conducted in the Structure program divided analyzed populations into two groups (SSR loci) and three groups (ISJ markers). Mantel test revealed correlations between the geographic distance and genetic diversity of Polish populations of P. patens for ISJ markers, but not for SSR markers. Conclusions The results of the present study suggest that ISJ markers can complement the analyses based on SSRs. However, neutral and adaptive markers should not be alternatively applied. Neutral microsatellite markers cannot depict the full range of genetic variation in a population because they do not enable to analyze functional variation. Although ISJ markers are less polymorphic, they can contribute to the reliability of analyses based on SSRs. PMID:27833793

Variation in the Oxytocin Receptor Gene Predicts Brain Region Specific Expression and Social Attachment

PubMed Central

King, Lanikea B.; Walum, Hasse; Inoue, Kiyoshi; Eyrich, Nicholas W.; Young, Larry J.

2015-01-01

Background Oxytocin (OXT) modulates several aspects of social behavior. Intranasal OXT is a leading candidate for treating social deficits in autism spectrum disorder (ASD) and common genetic variants in the human oxytocin receptor (OXTR) are associated with emotion recognition, relationship quality and ASD. Animal models have revealed that individual differences in Oxtr expression in the brain drive social behavior variation. Our understanding of how genetic variation contributes to brain OXTR expression is very limited. Methods We investigated Oxtr expression in monogamous prairie voles, which have a well characterized OXT system. We quantified brain region-specific levels of Oxtr mRNA and OXTR protein with established neuroanatomical methods. We used pyrosequencing to investigate allelic imbalance of Oxtr mRNA, a molecular signature of polymorphic genetic regulatory elements. We performed next-generation sequencing to discover variants in and near the Oxtr gene. We investigated social attachment using the partner preference test. Results Our allelic imbalance data demonstrates that genetic variants contribute to individual differences in Oxtr expression, but only in particular brain regions, including the nucleus accumbens (NAcc), where OXTR signaling facilitates social attachment. Next-generation sequencing identified one polymorphism in the Oxtr intron, near a putative cis-regulatory element, explaining 74% of the variance in striatal Oxtr expression specifically. Males homozygous for the high expressing allele display enhanced social attachment. Discussion Taken together, these findings provide convincing evidence for robust genetic influence on Oxtr expression and provide novel insights into how non-coding polymorphisms in the OXTR might influence individual differences in human social cognition and behavior PMID:26893121

Genes contributing to the development of alcoholism: an overview.

PubMed

Edenberg, Howard J

2012-01-01

Genetic factors (i.e., variations in specific genes) account for a substantial portion of the risk for alcoholism. However, identifying those genes and the specific variations involved is challenging. Researchers have used both case-control and family studies to identify genes related to alcoholism risk. In addition, different strategies such as candidate gene analyses and genome-wide association studies have been used. The strongest effects have been found for specific variants of genes that encode two enzymes involved in alcohol metabolism-alcohol dehydrogenase and aldehyde dehydrogenase. Accumulating evidence indicates that variations in numerous other genes have smaller but measurable effects.

Diversity of human copy number variation and multicopy genes.

PubMed

Sudmant, Peter H; Kitzman, Jacob O; Antonacci, Francesca; Alkan, Can; Malig, Maika; Tsalenko, Anya; Sampas, Nick; Bruhn, Laurakay; Shendure, Jay; Eichler, Evan E

2010-10-29

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

Intraspecific variation in social organization by genetic variation, developmental plasticity, social flexibility or entirely extrinsic factors.

PubMed

Schradin, Carsten

2013-05-19

Previously, it was widely believed that each species has a specific social organization, but we know now that many species show intraspecific variation in their social organization. Four different processes can lead to intraspecific variation in social organization: (i) genetic variation between individuals owing to local adaptation (between populations) or evolutionarily stable strategies within populations; (ii) developmental plasticity evolved in long-term (more than one generation) unpredictable and short-term (one generation) predictable environments, which is mediated by organizational physiological effects during early ontogeny; (iii) social flexibility evolved in highly unpredictable environments, which is mediated by activational physiological effects in adults; (iv) entirely extrinsic factors such as the death of a dominant breeder. Variation in social behaviour occurs between individuals in the case of genetic variation and developmental plasticity, but within individuals in the case of social flexibility. It is important to study intraspecific variation in social organization to understand the social systems of species because it reveals the mechanisms by which species can adapt to changing environments, offers a useful tool to study the ultimate and proximate causes of sociality, and is an interesting phenomenon by itself that needs scientific explanation.

Investigating the genetic and epigenetic basis of big biological questions with the parthenogenetic marbled crayfish: A review and perspectives.

PubMed

Vogt, Gunter

2018-03-01

In the last 15 years, considerable attempts have been undertaken to develop the obligately parthenogenetic marbled crayfish Procambarus virginalis as a new model in biology. Its main advantage is the production of large numbers of offspring that are genetically identical to the mother, making this crustacean particularly suitable for research in epigenetics. Now, a draft genome, transcriptome and genome-wide methylome are available opening new windows for research. In this article, I summarize the biological advantages and genomic and epigenetic features of marbled crayfish and, based on first promising data, discuss what this new model could contribute to answering of ''big'' biological questions. Genome mining is expected to reveal new insights into the genetic specificities of decapod crustaceans, the genetic basis of arthropod reproduction, moulting and immunity, and more general topics such as the genetic underpinning of adaptation to fresh water, omnivory, biomineralization, sexual system change, behavioural variation, clonal genome evolution, and resistance to cancer. Epigenetic investigations with the marbled crayfish can help clarifying the role of epigenetic mechanisms in gene regulation, tissue specification, adult stem cell regulation, cell ageing, organ regeneration and disease susceptibility. Marbled crayfish is further suitable to elucidate the relationship between genetic and epigenetic variation, the transgenerational inheritance of epigenetic signatures and the contribution of epigenetic phenotype variation to the establishment of social hierarchies, environmental adaptation and speciation. These issues can be tackled by experiments with highly standardized laboratory lineages, comparison of differently adapted wild populations and the generation of genetically and epigenetically edited strains.

Genetic and physiological bases for phenological responses to current and predicted climates

PubMed Central

Wilczek, A. M.; Burghardt, L. T.; Cobb, A. R.; Cooper, M. D.; Welch, S. M.; Schmitt, J.

2010-01-01

We are now reaching the stage at which specific genetic factors with known physiological effects can be tied directly and quantitatively to variation in phenology. With such a mechanistic understanding, scientists can better predict phenological responses to novel seasonal climates. Using the widespread model species Arabidopsis thaliana, we explore how variation in different genetic pathways can be linked to phenology and life-history variation across geographical regions and seasons. We show that the expression of phenological traits including flowering depends critically on the growth season, and we outline an integrated life-history approach to phenology in which the timing of later life-history events can be contingent on the environmental cues regulating earlier life stages. As flowering time in many plants is determined by the integration of multiple environmentally sensitive gene pathways, the novel combinations of important seasonal cues in projected future climates will alter how phenology responds to variation in the flowering time gene network with important consequences for plant life history. We discuss how phenology models in other systems—both natural and agricultural—could employ a similar framework to explore the potential contribution of genetic variation to the physiological integration of cues determining phenology. PMID:20819808

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

PubMed Central

Smoller, Jordan W

2016-01-01

Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories—posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders—for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene–environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research. PMID:26321314

Plant-microbe genomic systems optimization for energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hazen, Samuel P.

The overall objective of this project was to identify genetic variation within grasses that results in increased biomass yield and biofuel conversion efficiency. Improving energy crops hinges on identifying the genetic mechanisms underlying traits that benefit energy production. The exploitation of natural variation in plant species is an ideal approach to identify both the traits and the genes of interest in the production of biofuels. The specific goals of this project were to (1) quantify relevant genetic diversity for biofuel feedstock bioconversion efficiency and biomass accumulation, (2) identify genetic loci that control these traits, and (3) characterize genes for improvedmore » energy crop systems. Determining the key genetic contributors influencing biofuel traits is required in order to determine the viability of these traits as targets for improvement; only then will we be able to apply modern breeding practices and genetic engineering for the rapid improvement of feedstocks.« less

Mapping the genetic diversity of HLA haplotypes in the Japanese populations

PubMed Central

Saw, Woei-Yuh; Liu, Xuanyao; Khor, Chiea-Chuen; Takeuchi, Fumihiko; Katsuya, Tomohiro; Kimura, Ryosuke; Nabika, Toru; Ohkubo, Takayoshi; Tabara, Yasuharu; Yamamoto, Ken; Yokota, Mitsuhiro; Akiyama, Koichi; Asano, Hiroyuki; Asayama, Kei; Haga, Toshikazu; Hara, Azusa; Hirose, Takuo; Hosaka, Miki; Ichihara, Sahoko; Imai, Yutaka; Inoue, Ryusuke; Ishiguro, Aya; Isomura, Minoru; Isono, Masato; Kamide, Kei; Kato, Norihiro; Katsuya, Tomohiro; Kikuya, Masahiro; Kohara, Katsuhiko; Matsubara, Tatsuaki; Matsuda, Ayako; Metoki, Hirohito; Miki, Tetsuro; Murakami, Keiko; Nabika, Toru; Nakatochi, Masahiro; Ogihara, Toshio; Ohnaka, Keizo; Ohkubo, Takayoshi; Rakugi, Hiromi; Satoh, Michihiro; Shiwaku, Kunihiro; Sugimoto, Ken; Tabara, Yasuharu; Takami, Yoichi; Takayanagi, Ryoichi; Takeuchi, Fumihiko; Tsubota-Utsugi, Megumi; Yamamoto, Ken; Yamamoto, Koichi; Yamasaki, Masayuki; Yasui, Daisaku; Yokota, Mitsuhiro; Teo, Yik-Ying; Kato, Norihiro

2015-01-01

Japan has often been viewed as an Asian country that possesses a genetically homogenous community. The basis for partitioning the country into prefectures has largely been geographical, although cultural and linguistic differences still exist between some of the districts/prefectures, especially between Okinawa and the mainland prefectures. The Major Histocompatibility Complex (MHC) region has consistently emerged as the most polymorphic region in the human genome, harbouring numerous biologically important variants; nevertheless the presence of population-specific long haplotypes hinders the imputation of SNPs and classical HLA alleles. Here, we examined the extent of genetic variation at the MHC between eight Japanese populations sampled from Okinawa, and six other prefectures located in or close to the mainland of Japan, specifically focusing at the haplotypes observed within each population, and what the impact of any variation has on imputation. Our results indicated that Okinawa was genetically farther to the mainland Japanese than were Gujarati Indians from Tamil Indians, while the mainland Japanese from six prefectures were more homogeneous than between northern and southern Han Chinese. The distribution of haplotypes across Japan was similar, although imputation was most accurate for Okinawa and several mainland prefectures when population-specific panels were used as reference. PMID:26648100

Genetic regulation of the variation of circulating insulin-like growth factors and leptin in human pedigrees.

PubMed

Pantsulaia, Ia; Pantsulaia, I; Trofimov, Svetlana; Kobyliansky, Eugene; Livshits, Gregory

2005-07-01

Recent literature has shown that circulating levels of insulin-like growth factor I (IGF-I) and/or IGF binding proteins (IGF-BPs) may be of importance in the risk assessment of several chronic diseases including cancer, cardiovascular disease, diabetes mellitus and so on. The present study examined the extent of genetic and environmental influences on the populational variation of circulating IGF-I and IGF-BP-1 in apparently healthy and ethnically homogeneous white families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 563 individuals aged 18 to 80 years. Quantitative genetic analysis showed that the IGF-I variation was appreciably attributable to genetic effects (47.1% +/- 9.0%), whereas for IGF-BP-1, only 23.3% +/- 7.8% of the interindividual variation was explained by genetic determinants. Common familial environment factors contributed significantly only to IGF-BP-1 variation (23.3% +/- 7.8%). In addition, we examined the covariations between these molecules and between them and IGF-BP-3 and leptin that were previously studied in the same sample. The analysis revealed that the pleiotropic genetic effects were significant for 2 pairs of traits, namely for IGF-I and IGF-BP-3, and for IGF-BP-1 and leptin. The bivariate heritability estimates were 0.21 +/- 0.04 and 0.15 +/- 0.05. The common environmental factors were consistently a significant source of correlation between all pairs (barring IGF-I and leptin) of the studied molecules; they were the sole predictors of correlation between IGF-I and IGF-BP-1, and between IGF-BP-1 and IGF-BP-3. Our results affirm the existence of specific and common genetic pathways that in combination determine a substantial proportion of the circulating variation of these molecules.

Natural Variation in Resistance to Virus Infection in Dipteran Insects

PubMed Central

Palmer, William H.; Varghese, Finny S.

2018-01-01

The power and ease of Drosophila genetics and the medical relevance of mosquito-transmitted viruses have made dipterans important model organisms in antiviral immunology. Studies of virus–host interactions at the molecular and population levels have illuminated determinants of resistance to virus infection. Here, we review the sources and nature of variation in antiviral immunity and virus susceptibility in model dipteran insects, specifically the fruit fly Drosophila melanogaster and vector mosquitoes of the genera Aedes and Culex. We first discuss antiviral immune mechanisms and describe the virus-specificity of these responses. In the following sections, we review genetic and microbiota-dependent variation in antiviral immunity. In the final sections, we explore less well-studied sources of variation, including abiotic factors, sexual dimorphism, infection history, and endogenous viral elements. We borrow from work on other pathogen types and non-dipteran species when it parallels or complements studies in dipterans. Understanding natural variation in virus–host interactions may lead to the identification of novel restriction factors and immune mechanisms and shed light on the molecular determinants of vector competence. PMID:29522475

Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome

PubMed Central

Pinter, Stefan F.; Colognori, David; Beliveau, Brian J.; Sadreyev, Ruslan I.; Payer, Bernhard; Yildirim, Eda; Wu, Chao-ting; Lee, Jeannie T.

2015-01-01

In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease. PMID:25858912

Genome-wide genetic variation and comparison of fruit-associated traits between kumquat (Citrus japonica) and Clementine mandarin (Citrus clementina).

PubMed

Liu, Tian-Jia; Li, Yong-Ping; Zhou, Jing-Jing; Hu, Chun-Gen; Zhang, Jin-Zhi

2018-03-01

The comprehensive genetic variation of two citrus species were analyzed at genome and transcriptome level. A total of 1090 differentially expressed genes were found during fruit development by RNA-sequencing. Fruit size (fruit equatorial diameter) and weight (fresh weight) are the two most important components determining yield and consumer acceptability for many horticultural crops. However, little is known about the genetic control of these traits. Here, we performed whole-genome resequencing to reveal the comprehensive genetic variation of the fruit development between kumquat (Citrus japonica) and Clementine mandarin (Citrus clementina). In total, 5,865,235 single-nucleotide polymorphisms (SNPs) and 414,447 insertions/deletions (InDels) were identified in the two citrus species. Based on integrative analysis of genome and transcriptome of fruit, 640,801 SNPs and 20,733 InDels were identified. The features, genomic distribution, functional effect, and other characteristics of these genetic variations were explored. RNA-sequencing identified 1090 differentially expressed genes (DEGs) during fruit development of kumquat and Clementine mandarin. Gene Ontology revealed that these genes were involved in various molecular functional and biological processes. In addition, the genetic variation of 939 DEGs and 74 multiple fruit development pathway genes from previous reports were also identified. A global survey identified 24,237 specific alternative splicing events in the two citrus species and showed that intron retention is the most prevalent pattern of alternative splicing. These genome variation data provide a foundation for further exploration of citrus diversity and gene-phenotype relationships and for future research on molecular breeding to improve kumquat, Clementine mandarin and related species.

Genetics of Inflammatory Bowel Diseases

PubMed Central

McGovern, Dermot; Kugathasan, Subra; Cho, Judy H.

2015-01-01

In this Review, we provide an update on genome-wide association studies (GWAS) in inflammatory bowel disease (IBD). In addition, we summarize progress in defining the functional consequences of associated alleles for coding and non-coding genetic variation. In the small minority of loci where major association signals correspond to non-synonymous variation, we summarize studies defining their functional effects and implications for therapeutic targeting. Importantly, the large majority of GWAS-associated loci involve non-coding variation, many of which modulate levels of gene expression. Recent expression quantitative trait loci (eQTL) studies have established that expression of the large majority of human genes is regulated by non-coding genetic variation. Significant advances in defining the epigenetic landscape have demonstrated that IBD GWAS signals are highly enriched within cell-specific active enhancer marks. Studies in European ancestry populations have dominated the landscape of IBD genetics studies, but increasingly, studies in Asian and African-American populations are being reported. Common variation accounts for only a modest fraction of the predicted heritability and the role of rare genetic variation of higher effects (i.e. odds ratios markedly deviating from one) is increasingly being identified through sequencing efforts. These sequencing studies have been particularly productive in very-early onset, more severe cases. A major challenge in IBD genetics will be harnessing the vast array of genetic discovery for clinical utility, through emerging precision medicine initiatives. We discuss the rapidly evolving area of direct to consumer genetic testing, as well as the current utility of clinical exome sequencing, especially in very early onset, severe IBD cases. We summarize recent progress in the pharmacogenetics of IBD with respect of partitioning patient responses to anti-TNF and thiopurine therapies. Highly collaborative studies across research centers and across subspecialties and disciplines will be required to fully realize the promise of genetic discovery in IBD. PMID:26255561

Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers.

PubMed

Rawlings-Goss, Renata A; Campbell, Michael C; Tishkoff, Sarah A

2014-08-28

MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes. Genetic variation in 1524 miRNA genes was examined using whole genome sequencing (60x coverage) in a panel of 69 unrelated individuals from 14 global populations, including European, Asian and African populations. We identified 33 previously undescribed miRNA variants, and 31 miRNA containing variants that are globally population-differentiated in frequency between African and non-African populations (PD-miRNA). The top 1% of PD-miRNA were significantly enriched for regulation of genes involved in glucose/insulin metabolism and cell division (p < 10(-7)), most significantly the mitosis pathway, which is strongly linked to cancer onset. Overall, we identify 7 PD-miRNAs that are currently implicated as cancer biomarkers or diagnostics: hsa-mir-202, hsa-mir-423, hsa-mir-196a-2, hsa-mir-520h, hsa-mir-647, hsa-mir-943, and hsa-mir-1908. Notably, hsa-mir-202, a potential breast cancer biomarker, was found to show significantly high allele frequency differentiation at SNP rs12355840, which is known to affect miRNA expression levels in vivo and subsequently breast cancer mortality. MiRNA expression profiles represent a promising new category of disease biomarkers. However, population specific genetic variation can affect the prevalence and baseline expression of these miRNAs in diverse populations. Consequently, miRNA genetic and expression level variation among ethnic groups may be contributing in part to health disparities observed in multiple forms of cancer, specifically breast cancer, and will be an essential consideration when assessing the utility of miRNA biomarkers for the clinic.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation.

PubMed

Babak, Tomas; Garrett-Engele, Philip; Armour, Christopher D; Raymond, Christopher K; Keller, Mark P; Chen, Ronghua; Rohl, Carol A; Johnson, Jason M; Attie, Alan D; Fraser, Hunter B; Schadt, Eric E

2010-08-13

Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.

In Silico Detection of Sequence Variations Modifying Transcriptional Regulation

PubMed Central

Andersen, Malin C; Engström, Pär G; Lithwick, Stuart; Arenillas, David; Eriksson, Per; Lenhard, Boris; Wasserman, Wyeth W; Odeberg, Jacob

2008-01-01

Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation. PMID:18208319

Species delimitation and biogeography of two fir species (Abies) in central China: cytoplasmic DNA variation.

PubMed

Wang, J; Abbott, R J; Peng, Y L; Du, F K; Liu, J-Q

2011-10-01

It remains unclear how speciation history might contribute to species-specific variation and affect species delimitation. We examined concordance between cytoplasmic genetic variation and morphological taxonomy in two fir species, Abies chensiensis and A. fargesii, with overlapping distributions in central China. Range-wide genetic variation was investigated using mitochondrial (mt) and plastid (pt) DNA sequences, which contrast in their rates of gene flow. Four mtDNA haplotypes were recovered and showed no obvious species' bias in terms of relative frequency. In contrast, a high level of ptDNA variation was recorded in both species with 3 common ptDNA haplotypes shared between them and 21 rare ptDNA haplotypes specific to one or other species. We argue that the lack of concordance between morphological and molecular variation between the two fir species most likely reflects extensive ancestral polymorphism sharing for both forms of cytoplasmic DNA variation. It is feasible that a relatively fast mutation rate for ptDNA contributed to the production of many species-specific ptDNA haplotypes, which remained rare due to insufficient time passing for their spread and fixation in either species, despite high levels of intraspecific ptDNA gene flow. Our phylogeographic analyses further suggest that polymorphisms in both organelle genomes most likely originated during and following glacial intervals preceding the last glacial maximum, when species distributions became fragmented into several refugia and then expanded in range across central China.

High level of molecular and phenotypic biodiversity in Jatropha curcas from Central America compared to Africa, Asia and South America

PubMed Central

2014-01-01

Background The main bottleneck to elevate jatropha (Jatropha curcas L.) from a wild species to a profitable biodiesel crop is the low genetic and phenotypic variation found in different regions of the world, hampering efficient plant breeding for productivity traits. In this study, 182 accessions from Asia (91), Africa (35), South America (9) and Central America (47) were evaluated at genetic and phenotypic level to find genetic variation and important traits for oilseed production. Results Genetic variation was assessed with SSR (Simple Sequence Repeat), TRAP (Target Region Amplification Polymorphism) and AFLP (Amplified fragment length polymorphism) techniques. Phenotypic variation included seed morphological characteristics, seed oil content and fatty acid composition and early growth traits. Jaccard’s similarity and cluster analysis by UPGM (Unweighted Paired Group Method) with arithmetic mean and PCA (Principle Component Analysis) indicated higher variability in Central American accessions compared to Asian, African and South American accessions. Polymorphism Information Content (PIC) values ranged from 0 to 0.65. In the set of Central American accessions. PIC values were higher than in other regions. Accessions from the Central American population contain alleles that were not found in the accessions from other populations. Analysis of Molecular Variance (AMOVA; P < 0.0001) indicated high genetic variation within regions (81.7%) and low variation across regions (18.3%). A high level of genetic variation was found on early growth traits and on components of the relative growth rate (specific leaf area, leaf weight, leaf weight ratio and net assimilation rate) as indicated by significant differences between accessions and by the high heritability values (50–88%). The fatty acid composition of jatropha oil significantly differed (P < 0.05) between regions. Conclusions The pool of Central American accessions showed very large genetic variation as assessed by DNA-marker variation compared to accessions from other regions. Central American accessions also showed the highest phenotypic variation and should be considered as the most important source for plant breeding. Some variation in early growth traits was found within a group of accessions from Asia and Africa, while these accessions did not differ in a single DNA-marker, possibly indicating epigenetic variation. PMID:24666927

[Genetic mutation databases: stakes and perspectives for orphan genetic diseases].

PubMed

Humbertclaude, V; Tuffery-Giraud, S; Bareil, C; Thèze, C; Paulet, D; Desmet, F-O; Hamroun, D; Baux, D; Girardet, A; Collod-Béroud, G; Khau Van Kien, P; Roux, A-F; des Georges, M; Béroud, C; Claustres, M

2010-10-01

New technologies, which constantly become available for mutation detection and gene analysis, have contributed to an exponential rate of discovery of disease genes and variation in the human genome. The task of collecting and documenting this enormous amount of data in genetic databases represents a major challenge for the future of biological and medical science. The Locus Specific Databases (LSDBs) are so far the most efficient mutation databases. This review presents the main types of databases available for the analysis of mutations responsible for genetic disorders, as well as open perspectives for new therapeutic research or challenges for future medicine. Accurate and exhaustive collection of variations in human genomes will be crucial for research and personalized delivery of healthcare. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Joint genetic analysis of hippocampal size in mouse and human identifies a novel gene linked to neurodegenerative disease.

PubMed

Ashbrook, David G; Williams, Robert W; Lu, Lu; Stein, Jason L; Hibar, Derrek P; Nichols, Thomas E; Medland, Sarah E; Thompson, Paul M; Hager, Reinmar

2014-10-03

Variation in hippocampal volume has been linked to significant differences in memory, behavior, and cognition among individuals. To identify genetic variants underlying such differences and associated disease phenotypes, multinational consortia such as ENIGMA have used large magnetic resonance imaging (MRI) data sets in human GWAS studies. In addition, mapping studies in mouse model systems have identified genetic variants for brain structure variation with great power. A key challenge is to understand how genetically based differences in brain structure lead to the propensity to develop specific neurological disorders. We combine the largest human GWAS of brain structure with the largest mammalian model system, the BXD recombinant inbred mouse population, to identify novel genetic targets influencing brain structure variation that are linked to increased risk for neurological disorders. We first use a novel cross-species, comparative analysis using mouse and human genetic data to identify a candidate gene, MGST3, associated with adult hippocampus size in both systems. We then establish the coregulation and function of this gene in a comprehensive systems-analysis. We find that MGST3 is associated with hippocampus size and is linked to a group of neurodegenerative disorders, such as Alzheimer's.

Indication for Co-evolution of Lactobacillus johnsonii with its hosts

PubMed Central

2012-01-01

Background The intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts. Results A wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice. Conclusions Our typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria. PMID:22827843

Indication for Co-evolution of Lactobacillus johnsonii with its hosts.

PubMed

Buhnik-Rosenblau, Keren; Matsko-Efimov, Vera; Jung, Minju; Shin, Heuynkil; Danin-Poleg, Yael; Kashi, Yechezkel

2012-07-25

The intestinal microbiota, composed of complex bacterial populations, is host-specific and affected by environmental factors as well as host genetics. One important bacterial group is the lactic acid bacteria (LAB), which include many health-promoting strains. Here, we studied the genetic variation within a potentially probiotic LAB species, Lactobacillus johnsonii, isolated from various hosts. A wide survey of 104 fecal samples was carried out for the isolation of L. johnsonii. As part of the isolation procedure, terminal restriction fragment length polymorphism (tRFLP) was performed to identify L. johnsonii within a selected narrow spectrum of fecal LAB. The tRFLP results showed host specificity of two bacterial species, the Enterococcus faecium species cluster and Lactobacillus intestinalis, to different host taxonomic groups while the appearance of L. johnsonii and E. faecalis was not correlated with any taxonomic group. The survey ultimately resulted in the isolation of L. johnsonii from few host species. The genetic variation among the 47 L. johnsonii strains isolated from the various hosts was analyzed based on variation at simple sequence repeats (SSR) loci and multi-locus sequence typing (MLST) of conserved hypothetical genes. The genetic relationships among the strains inferred by each of the methods were similar, revealing three different clusters of L. johnsonii strains, each cluster consisting of strains from a different host, i.e. chickens, humans or mice. Our typing results support phylogenetic separation of L. johnsonii strains isolated from different animal hosts, suggesting specificity of L. johnsonii strains to their hosts. Taken together with the tRFLP results, that indicated the association of specific LAB species with the host taxonomy, our study supports co-evolution of the host and its intestinal lactic acid bacteria.

A population genomics approach shows widespread geographical distribution of cryptic genomic forms of the symbiotic fungus Rhizophagus irregularis.

PubMed

Savary, Romain; Masclaux, Frédéric G; Wyss, Tania; Droh, Germain; Cruz Corella, Joaquim; Machado, Ana Paula; Morton, Joseph B; Sanders, Ian R

2018-01-01

Arbuscular mycorrhizal fungi (AMF; phylum Gomeromycota) associate with plants forming one of the most successful microbe-plant associations. The fungi promote plant diversity and have a potentially important role in global agriculture. Plant growth depends on both inter- and intra-specific variation in AMF. It was recently reported that an unusually large number of AMF taxa have an intercontinental distribution, suggesting long-distance gene flow for many AMF species, facilitated by either long-distance natural dispersal mechanisms or human-assisted dispersal. However, the intercontinental distribution of AMF species has been questioned because the use of very low-resolution markers may be unsuitable to detect genetic differences among geographically separated AMF, as seen with some other fungi. This has been untestable because of the lack of population genomic data, with high resolution, for any AMF taxa. Here we use phylogenetics and population genomics to test for intra-specific variation in Rhizophagus irregularis, an AMF species for which genome sequence information already exists. We used ddRAD sequencing to obtain thousands of markers distributed across the genomes of 81 R. irregularis isolates and related species. Based on 6 888 variable positions, we observed significant genetic divergence into four main genetic groups within R. irregularis, highlighting that previous studies have not captured underlying genetic variation. Despite considerable genetic divergence, surprisingly, the variation could not be explained by geographical origin, thus also supporting the hypothesis for at least one AMF species of widely dispersed AMF genotypes at an intercontinental scale. Such information is crucial for understanding AMF ecology, and how these fungi can be used in an environmentally safe way in distant locations.

Genetic variation in transmission success of the Lyme borreliosis pathogen Borrelia afzelii.

PubMed

Tonetti, Nicolas; Voordouw, Maarten J; Durand, Jonas; Monnier, Séverine; Gern, Lise

2015-04-01

The vector-to-host and host-to-vector transmission steps are the two critical events that define the life cycle of any vector-borne pathogen. We expect negative genetic correlations between these two transmission phenotypes, if parasite genotypes specialized at invading the vector are less effective at infecting the vertebrate host and vice versa. We used the tick-borne bacterium Borrelia afzelii, a causative agent of Lyme borreliosis in Europe, to test whether genetic trade-offs exist between tick-to-host, systemic (host-to-tick), and a third mode of co-feeding (tick-to-tick) transmission. We worked with six strains of B. afzelii that were differentiated according to their ospC gene. We compared the three components of transmission among the B. afzelii strains using laboratory rodents as the vertebrate host and a laboratory colony of Ixodes ricinus as the tick vector. We used next generation matrix models to combine these transmission components into a single estimate of the reproductive number (R0) for each B. afzelii strain. We also tested whether these strain-specific estimates of R0 were correlated with the strain-specific frequencies in the field. We found significant genetic variation in the three transmission components among the B. afzelii strains. This is the first study to document genetic variation in co-feeding transmission for any tick-borne pathogen. We found no evidence of trade-offs as the three pairwise correlations of the transmission rates were all positive. The R0 values from our laboratory study explained 45% of the variation in the frequencies of the B. afzelii ospC strains in the field. Our study suggests that laboratory estimates of pathogen fitness can predict the distribution of pathogen strains in nature. Copyright © 2015 Elsevier GmbH. All rights reserved.

Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors.

PubMed

Choi, Min-Koo; Shin, Ho Jung; Choi, Young-Lim; Deng, Jian-Wei; Shin, Jae-Gook; Song, Im-Sook

2011-01-01

The purpose of this study was to investigate the effect of genetic variations in organic anion-transporting polypeptide 1B1 (OATP1B1) and Na(+)/taurocholate co-transporting polypeptide (NTCP) on the uptake of various statins having different affinities for these transporters. The functional activities and simultaneous expression of NTCP and OATP1B1 were confirmed by the uptake of taurocholate and estrone-3-sulphate as representative substrates for NTCP and OATP1B1, respectively, and by an immunofluorescence analysis. The substrate specificities of NTCP and OATP1B1 for statins and the effects of genetic variations on the uptake of rosuvastatin, pitavastatin, and atorvastatin were measured. Based on the K(m) values and intrinsic clearances of the three statins, pitavastatin was taken up more efficiently than rosuvastatin and atorvastatin by OATP1B1. Consequently, the cellular accumulation of pitavastatin was modulated according to the genetic variation of OATP1B1 (OATP1B1*15), rather than NTCP*2. In contrast, NTCP*2 displayed greater transport of atorvastatin and rosuvastatin, compared with NTCP wild type. Thus, the measurements of decreased rosuvastatin and atorvastatin transport by OATP1B1*15 were confounded by the presence of NTCP and its genetic variant, NTCP*2. In conclusion, the functional consequences of genetic variants of NTCP and OATP1B1 may be different for various statins, depending on the substrate specificity of the OATP1B1 and NTCP transporters.

Chemical and Mechanical Defenses Vary among Maternal Lines and Leaf Ages in Verbascum thapsus L. (Scrophulariaceae) and Reduce Palatability to a Generalist Insect

PubMed Central

Alba, Christina; Bowers, M. Deane; Blumenthal, Dana; Hufbauer, Ruth A.

2014-01-01

Intra-specific variation in host-plant quality affects herbivore foraging decisions and, in turn, herbivore foraging decisions mediate plant fitness. In particular, variation in defenses against herbivores, both among and within plants, shapes herbivore behavior. If variation in defenses is genetically based, it can respond to natural selection by herbivores. We quantified intra-specific variation in iridoid glycosides, trichome length, and leaf strength in common mullein (Verbascum thapsus L, Scrophulariaceae) among maternal lines within a population and among leaves within plants, and related this variation to feeding preferences of a generalist herbivore, Trichopulsia ni Hübner. We found significant variation in all three defenses among maternal lines, with T. ni preferring plants with lower investment in chemical, but not mechanical, defense. Within plants, old leaves had lower levels of all defenses than young leaves, and were strongly preferred by T. ni. Caterpillars also preferred leaves with trichomes removed to leaves with trichomes intact. Differences among maternal lines indicate that phenotypic variation in defenses likely has a genetic basis. Furthermore, these results reveal that the feeding behaviors of T. ni map onto variation in plant defense in a predictable way. This work highlights the importance of variation in host-plant quality in driving interactions between plants and their herbivores. PMID:25127229

Does the central dogma still stand?

PubMed Central

2012-01-01

Abstract Prions are agents of analog, protein conformation-based inheritance that can confer beneficial phenotypes to cells, especially under stress. Combined with genetic variation, prion-mediated inheritance can be channeled into prion-independent genomic inheritance. Latest screening shows that prions are common, at least in fungi. Thus, there is non-negligible flow of information from proteins to the genome in modern cells, in a direct violation of the Central Dogma of molecular biology. The prion-mediated heredity that violates the Central Dogma appears to be a specific, most radical manifestation of the widespread assimilation of protein (epigenetic) variation into genetic variation. The epigenetic variation precedes and facilitates genetic adaptation through a general ‘look-ahead effect’ of phenotypic mutations. This direction of the information flow is likely to be one of the important routes of environment-genome interaction and could substantially contribute to the evolution of complex adaptive traits. Reviewers This article was reviewed by Jerzy Jurka, Pierre Pontarotti and Juergen Brosius. For the complete reviews, see the Reviewers’ Reports section. PMID:22913395

Heritability of circulating growth factors involved in the angiogenesis in healthy human population.

PubMed

Pantsulaia, I; Trofimov, S; Kobyliansky, E; Livshits, G

2004-09-21

The present study examined the extent of genetic and environmental influences on the populational variation of circulating growth factors (VEGF, EGF) involved in angiogenesis in healthy and ethnically homogeneous Caucasian families. The plasma levels of each of the studied biochemical indices were determined by enzyme-linked immunoassay in 478 healthy individuals aged 18-75 years. Quantitative genetic analysis showed that the VEGF and EGF variation was appreciably attributable to genetic effects, with heritability estimates of 79.9% and 48.4%, respectively. Yet, common environmental factors, shared by members of the same household, also played a significant role (P < 0.01) and explained between 20.1% and 32.6% of the variation. The present study additionally examined the covariations between these molecules and either transforming growth factor-beta 1 (TGF-beta 1) or tissue inhibitors of matrix metalloproteinases 1 (TIMP-1), likewise relevant for angiogenesis. Bivariate analysis revealed significant phenotypic correlations (P < 0.002) between all pairs of variables, thus indicating the possible existence of common genetic and environmental factors. The analysis suggested that the pleiotropic genetic effects were consistently the primary (or even the sole) source of correlation between all pairs of studied molecules. The results of our study affirm the existence of specific and common genetic pathways that commonly determine the greater part of the circulating variation of these molecules.

Sex-dependent selection differentially shapes genetic variation on and off the guppy Y chromosome.

PubMed

Postma, Erik; Spyrou, Nicolle; Rollins, Lee Ann; Brooks, Robert C

2011-08-01

Because selection is often sex-dependent, alleles can have positive effects on fitness in one sex and negative effects in the other, resulting in intralocus sexual conflict. Evolutionary theory predicts that intralocus sexual conflict can drive the evolution of sex limitation, sex-linkage, and sex chromosome differentiation. However, evidence that sex-dependent selection results in sex-linkage is limited. Here, we formally partition the contribution of Y-linked and non-Y-linked quantitative genetic variation in coloration, tail, and body size of male guppies (Poecilia reticulata)-traits previously implicated as sexually antagonistic. We show that these traits are strongly genetically correlated, both on and off the Y chromosome, but that these correlations differ in sign and magnitude between both parts of the genome. As predicted, variation in attractiveness was found to be associated with the Y-linked, rather than with the non-Y-linked component of genetic variation in male ornamentation. These findings show how the evolution of Y-linkage may be able to resolve sexual conflict. More generally, they provide unique insight into how sex-specific selection has the potential to differentially shape the genetic architecture of fitness traits across different parts of the genome. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Heritabilities of somatotype components in a population from rural Mozambique.

PubMed

Saranga, Sílvio Pedro José; Prista, António; Nhantumbo, Leonardo; Beunen, Gaston; Rocha, Jorge; Williams-Blangero, Sarah; Maia, José A

2008-01-01

There have been few genetic studies of normal variation in body size and composition conducted in Africa. In particular, the genetic determinants of somatotype remain to be established for an African population. (1) To estimate the heritabilities of aspects of somatotype and (2) to compare the quantitative genetic effects in an African population to those that have been assessed in European and American populations. The sample composed of 329 subjects (173 males and 156 females) aged 7-17 years, belonging to 132 families. The sibships in the sample ranged in size from two to seven individuals. All sampled individuals were residents of the Calanga region, an area located to the north of Maputo in Mozambique. Somatotype was assessed using the Heath-Carter technique. Herit abilities were estimated using SAGE software. Moderate heritabilities were determined for each trait. Between 30 and 40% of the variation in each somatotype measure was attributable to genetic factors. The heritability of ectomorphy was 31%. Mesomorphy was similarly moderately heritable, with approximately 30% of the variationattributable to genetic factors. The heritability of endomorph was higher in the Calanga population (h(2) = 0.40). Quantitative genetic analyses of somatotype variation among siblings indicate that genetic factors significantly influence endomorphy, mesomorhpy, and ectomorphy. However, environmental factors also have significant effects on the variation in physique present in the population of Calanga. Lack of proper nutrition, housing, medical assistance, and primary health care, together with very demanding and sex-specific daily chores may contribute to the environmental effects on these traits.

Contrasting Genomic Diversity in Two Closely Related Postharvest Pathogens: Penicillium digitatum and Penicillium expansum.

PubMed

Julca, Irene; Droby, Samir; Sela, Noa; Marcet-Houben, Marina; Gabaldón, Toni

2015-12-14

Penicillium digitatum and Penicillium expansum are two closely related fungal plant pathogens causing green and blue mold in harvested fruit, respectively. The two species differ in their host specificity, being P. digitatum restricted to citrus fruits and P. expansum able to infect a wide range of fruits after harvest. Although host-specific Penicillium species have been found to have a smaller gene content, it is so far unclear whether these different host specificities impact genome variation at the intraspecific level. Here we assessed genome variation across four P. digitatum and seven P. expansum isolates from geographically distant regions. Our results show very high similarity (average 0.06 SNPs [single nucleotide polymorphism] per kb) between globally distributed isolates of P. digitatum pointing to a recent expansion of a single lineage. This low level of genetic variation found in our samples contrasts with the higher genetic variability observed in the similarly distributed P. expansum isolates (2.44 SNPs per kb). Patterns of polymorphism in P. expansum indicate that recombination exists between genetically diverged strains. Consistent with the existence of sexual recombination and heterothallism, which was unknown for this species, we identified the two alternative mating types in different P. expansum isolates. Patterns of polymorphism in P. digitatum indicate a recent clonal population expansion of a single lineage that has reached worldwide distribution. We suggest that the contrasting patterns of genomic variation between the two species reflect underlying differences in population dynamics related with host specificities and related agricultural practices. It should be noted, however, that this results should be confirmed with a larger sampling of strains, as new strains may broaden the diversity so far found in P. digitatum. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Y-chromosome and mtDNA variation confirms independent domestications and directional hybridization in South American camelids.

PubMed

Marín, J C; Romero, K; Rivera, R; Johnson, W E; González, B A

2017-10-01

Investigations of genetic diversity and domestication in South American camelids (SAC) have relied on autosomal microsatellite and maternally-inherited mitochondrial data. We present the first integrated analysis of domestic and wild SAC combining male and female sex-specific markers (male specific Y-chromosome and female-specific mtDNA sequence variation) to assess: (i) hypotheses about the origin of domestic camelids, (ii) directionality of introgression among domestic and/or wild taxa as evidence of hybridization and (iii) currently recognized subspecies patterns. Three male-specific Y-chromosome markers and control region sequences of mitochondrial DNA are studied here. Although no sequence variation was found in SRY and ZFY, there were seven variable sites in DBY generating five haplotypes on the Y-chromosome. The haplotype network showed clear separation between haplogroups of guanaco-llama and vicuña-alpaca, indicating two genetically distinct patrilineages with near absence of shared haplotypes between guanacos and vicuñas. Although we document some examples of directional hybridization, the patterns strongly support the hypothesis that llama (Lama glama) is derived from guanaco (Lama guanicoe) and the alpaca (Vicugna pacos) from vicuña (Vicugna vicugna). Within male guanacos we identified a haplogroup formed by three haplotypes with different geographical distributions, the northernmost of which (Peru and northern Chile) was also observed in llamas, supporting the commonly held hypothesis that llamas were domesticated from the northernmost populations of guanacos (L. g. cacilensis). Southern guanacos shared the other two haplotypes. A second haplogroup, consisting of two haplotypes, was mostly present in vicuñas and alpacas. However, Y-chromosome variation did not distinguish the two subspecies of vicuñas. © 2017 Stichting International Foundation for Animal Genetics.

The Application of Structural Equation Modeling to Maternal Ratings of Twins' Behavior and Emotional Problems.

ERIC Educational Resources Information Center

Silberg, Judy L.; And Others

1994-01-01

Applied structural equation modeling to twin data to assess impact of genetic and environmental factors on children's behavioral and emotional functioning. Applied models to maternal ratings of behavior of 515 monozygotic and 749 dizygotic twin pairs. Importance of genetic, shared, and specific environmental factors for explaining variation was…

Technical approaches for mouse models of human disease.

PubMed

Justice, Monica J; Siracusa, Linda D; Stewart, A Francis

2011-05-01

The mouse is the leading organism for disease research. A rich resource of genetic variation occurs naturally in inbred and special strains owing to spontaneous mutations. However, one can also obtain desired gene mutations by using the following processes: targeted mutations that eliminate function in the whole organism or in a specific tissue; forward genetic screens using chemicals or transposons; or the introduction of exogenous transgenes as DNAs, bacterial artificial chromosomes (BACs) or reporter constructs. The mouse is the only mammal that provides such a rich resource of genetic diversity coupled with the potential for extensive genome manipulation, and is therefore a powerful application for modeling human disease. This poster review outlines the major genome manipulations available in the mouse that are used to understand human disease: natural variation, reverse genetics, forward genetics, transgenics and transposons. Each of these applications will be essential for understanding the diversity that is being discovered within the human population.

Genetic variation at microsatellite loci in the tropical herb Aphelandra aurantiaca (Acanthaceae).

PubMed

Suárez-Montes, Pilar; Tapia-López, Rosalinda; Núñez-Farfán, Juan

2015-11-01

To assess the effect of forest fragmentation on genetic variation and population structure of Aphelandra aurantiaca (Acanthaceae), a tropical and ornamental herbaceous perennial plant, we developed the first microsatellite primers for the species. Fourteen microsatellite markers were isolated and characterized from A. aurantiaca genomic libraries enriched for di-, tri-, and tetranucleotide repeat motifs. Polymorphism was evaluated in 107 individuals from four natural populations. Twelve out of 14 genetic markers were polymorphic. The number of alleles per locus ranged from two to 12, and the observed and expected heterozygosities ranged from 0.22 to 0.96 and from 0.20 to 0.87, respectively. Fixation indices ranged from -0.41 to 0.44. These newly developed microsatellite markers for A. aurantiaca will be useful for future population genetic studies, specifically to detect the possible loss of genetic diversity due to habitat fragmentation.

Marker-Based Estimates Reveal Significant Non-additive Effects in Clonally Propagated Cassava (Manihot esculenta): Implications for the Prediction of Total Genetic Value and the Selection of Varieties.

PubMed

Wolfe, Marnin D; Kulakow, Peter; Rabbi, Ismail Y; Jannink, Jean-Luc

2016-08-31

In clonally propagated crops, non-additive genetic effects can be effectively exploited by the identification of superior genetic individuals as varieties. Cassava (Manihot esculenta Crantz) is a clonally propagated staple food crop that feeds hundreds of millions. We quantified the amount and nature of non-additive genetic variation for three key traits in a breeding population of cassava from sub-Saharan Africa using additive and non-additive genome-wide marker-based relationship matrices. We then assessed the accuracy of genomic prediction for total (additive plus non-additive) genetic value. We confirmed previous findings based on diallel populations, that non-additive genetic variation is significant for key cassava traits. Specifically, we found that dominance is particularly important for root yield and epistasis contributes strongly to variation in CMD resistance. Further, we showed that total genetic value predicted observed phenotypes more accurately than additive only models for root yield but not for dry matter content, which is mostly additive or for CMD resistance, which has high narrow-sense heritability. We address the implication of these results for cassava breeding and put our work in the context of previous results in cassava, and other plant and animal species. Copyright © 2016 Author et al.

Contrasting modes and tempos of venom expression evolution in two snake species.

PubMed

Margres, Mark J; McGivern, James J; Seavy, Margaret; Wray, Kenneth P; Facente, Jack; Rokyta, Darin R

2015-01-01

Selection is predicted to drive diversification within species and lead to local adaptation, but understanding the mechanistic details underlying this process and thus the genetic basis of adaptive evolution requires the mapping of genotype to phenotype. Venom is complex and involves many genes, but the specialization of the venom gland toward toxin production allows specific transcripts to be correlated with specific toxic proteins, establishing a direct link from genotype to phenotype. To determine the extent of expression variation and identify the processes driving patterns of phenotypic diversity, we constructed genotype-phenotype maps and compared range-wide toxin-protein expression variation for two species of snake with nearly identical ranges: the eastern diamondback rattlesnake (Crotalus adamanteus) and the eastern coral snake (Micrurus fulvius). We detected significant expression variation in C. adamanteus, identified the specific loci associated with population differentiation, and found that loci expressed at all levels contributed to this divergence. Contrary to expectations, we found no expression variation in M. fulvius, suggesting that M. fulvius populations are not locally adapted. Our results not only linked expression variation at specific loci to divergence in a polygenic, complex trait but also have extensive conservation and biomedical implications. C. adamanteus is currently a candidate for federal listing under the Endangered Species Act, and the loss of any major population would result in the irrevocable loss of a unique venom phenotype. The lack of variation in M. fulvius has significant biomedical application because our data will assist in the development of effective antivenom for this species. Copyright © 2015 by the Genetics Society of America.

Response of predatory mites to a herbivore-induced plant volatile: genetic variation for context-dependent behaviour.

PubMed

Sznajder, Beata; Sabelis, Maurice W; Egas, Martijn

2010-07-01

Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators' responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles.

Response of Predatory Mites to a Herbivore-Induced Plant Volatile: Genetic Variation for Context-Dependent Behaviour

PubMed Central

Sabelis, Maurice W.; Egas, Martijn

2010-01-01

Plants infested with herbivores release specific volatile compounds that are known to recruit natural enemies. The response of natural enemies to these volatiles may be either learned or genetically determined. We asked whether there is genetic variation in the response of the predatory mite Phytoseiulus persimilis to methyl salicylate (MeSa). MeSa is a volatile compound consistently produced by plants being attacked by the two-spotted spider mite, the prey of P. persimilis. We predicted that predators express genetically determined responses during long-distance migration where previously learned associations may have less value. Additionally, we asked whether these responses depend on odors from uninfested plants as a background to MeSa. To infer a genetic basis, we analyzed the variation in response to MeSa among iso-female lines of P. persimilis by using choice-tests that involved either (1) MeSa presented as a single compound or (2) MeSa with background-odor from uninfested lima bean plants. These tests were conducted for starved and satiated predators, i.e., two physiological states, one that approximates migration and another that mimics local patch exploration. We found variation among iso-female lines in the responses to MeSa, thus showing genetic variation for this behavior. The variation was more pronounced in the starved predators, thus indicating that P. persimilis relies on innate preferences when migrating. Background volatiles of uninfested plants changed the predators’ responses to MeSa in a manner that depended on physiological state and iso-female line. Thus, it is possible to select for context-dependent behavioral responses of natural enemies to plant volatiles. PMID:20574785

Dissection of expression-quantitative trait locus and allele specificity using a haploid/diploid plant system - insights into compensatory evolution of transcriptional regulation within populations.

PubMed

Verta, Jukka-Pekka; Landry, Christian R; MacKay, John

2016-07-01

Regulation of gene expression plays a central role in translating genotypic variation into phenotypic variation. Dissection of the genetic basis of expression variation is key to understanding how expression regulation evolves. Such analyses remain challenging in contexts where organisms are outbreeding, highly heterozygous and long-lived such as in the case of conifer trees. We developed an RNA sequencing (RNA-seq)-based approach for both expression-quantitative trait locus (eQTL) mapping and the detection of cis-acting (allele-specific) vs trans-acting (non-allele-specific) eQTLs. This method can be potentially applied to many conifers. We used haploid and diploid meiotic seed tissues of a single self-fertilized white spruce (Picea glauca) individual to dissect eQTLs according to linkage and allele specificity. The genetic architecture of local eQTLs linked to the expressed genes was particularly complex, consisting of cis-acting, trans-acting and, surprisingly, compensatory cis-trans effects. These compensatory effects influence expression in opposite directions and are neutral when combined in homozygotes. Nearly half of local eQTLs were under compensation, indicating that close linkage between compensatory cis-trans factors is common in spruce. Compensated genes were overrepresented in developmental and cell organization functions. Our haploid-diploid eQTL analysis in spruce revealed that compensatory cis-trans eQTLs segregate within populations and evolve in close genetic linkage. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Genetic variation in Northern Thailand Hill Tribes: origins and relationships with social structure and linguistic differences

PubMed Central

Besaggio, Davide; Fuselli, Silvia; Srikummool, Metawee; Kampuansai, Jatupol; Castrì, Loredana; Tyler-Smith, Chris; Seielstad, Mark; Kangwanpong, Daoroong; Bertorelle, Giorgio

2007-01-01

Background Ethnic minorities in Northern Thailand, often referred to as Hill Tribes, are considered an ideal model to study the different genetic impact of sex-specific migration rates expected in matrilocal (women remain in their natal villages after the marriage and men move to their wife's village) and patrilocal societies (the opposite is true). Previous studies identified such differences, but little is known about the possible interaction with another cultural factor that may potentially affect genetic diversity, i.e. linguistic differences. In addition, Hill Tribes started to migrate to Thailand in the last centuries from different Northern areas, but the history of these migrations, the level of genetic legacy with their places of origin, and the possible confounding effects related to this migration history in the patterns of genetic diversity, have not been analysed yet. Using both original and published data on the Hill Tribes and several other Asian populations, we focused on all these aspects. Results Genetic variation within population at mtDNA is lower in matrilocal, compared to patrilocal, tribes. The opposite is true for Y-chromosome microsatellites within the Sino-Tibetan linguistic family, but Hmong-Mien speaking patrilocal groups have a genetic diversity very similar to the matrilocal samples. Population divergence ranges between 5% and 14% at mtDNA sequences, and between 5% and 36% at Y- chromosomes STRs, and follows the sex-specific differences expected in patrilocal and matrilocal tribes. On the average, about 2 men and 14 women, and 4 men and 4 women, are exchanged in patrilocal and matrilocal tribes every generation, respectively. Most of the Hill Tribes in Thailand seem to preserve a genetic legacy with their likely geographic origin, with children adoption probably affecting this pattern in one tribe. Conclusion Overall, the sex specific genetic signature of different postmarital habits of residence in the Hill Tribes is robust. However, specific perturbations related to linguistic differences, population specific traits, and the complex migratory history of these groups, can be identified. Additional studies in different populations are needed, especially to obtain more precise estimates of the migration parameters. PMID:17767728

Genetic variation in Northern Thailand Hill Tribes: origins and relationships with social structure and linguistic differences.

PubMed

Besaggio, Davide; Fuselli, Silvia; Srikummool, Metawee; Kampuansai, Jatupol; Castrì, Loredana; Tyler-Smith, Chris; Seielstad, Mark; Kangwanpong, Daoroong; Bertorelle, Giorgio

2007-08-16

Ethnic minorities in Northern Thailand, often referred to as Hill Tribes, are considered an ideal model to study the different genetic impact of sex-specific migration rates expected in matrilocal (women remain in their natal villages after the marriage and men move to their wife's village) and patrilocal societies (the opposite is true). Previous studies identified such differences, but little is known about the possible interaction with another cultural factor that may potentially affect genetic diversity, i.e. linguistic differences. In addition, Hill Tribes started to migrate to Thailand in the last centuries from different Northern areas, but the history of these migrations, the level of genetic legacy with their places of origin, and the possible confounding effects related to this migration history in the patterns of genetic diversity, have not been analysed yet. Using both original and published data on the Hill Tribes and several other Asian populations, we focused on all these aspects. Genetic variation within population at mtDNA is lower in matrilocal, compared to patrilocal, tribes. The opposite is true for Y-chromosome microsatellites within the Sino-Tibetan linguistic family, but Hmong-Mien speaking patrilocal groups have a genetic diversity very similar to the matrilocal samples. Population divergence ranges between 5% and 14% at mtDNA sequences, and between 5% and 36% at Y-chromosomes STRs, and follows the sex-specific differences expected in patrilocal and matrilocal tribes. On the average, about 2 men and 14 women, and 4 men and 4 women, are exchanged in patrilocal and matrilocal tribes every generation, respectively. Most of the Hill Tribes in Thailand seem to preserve a genetic legacy with their likely geographic origin, with children adoption probably affecting this pattern in one tribe. Overall, the sex specific genetic signature of different postmarital habits of residence in the Hill Tribes is robust. However, specific perturbations related to linguistic differences, population specific traits, and the complex migratory history of these groups, can be identified. Additional studies in different populations are needed, especially to obtain more precise estimates of the migration parameters.

Functional Incompatibility between the Generic NF-κB Motif and a Subtype-Specific Sp1III Element Drives the Formation of the HIV-1 Subtype C Viral Promoter

PubMed Central

Verma, Anjali; Rajagopalan, Pavithra; Lotke, Rishikesh; Varghese, Rebu; Selvam, Deepak; Kundu, Tapas K.

2016-01-01

ABSTRACT Of the various genetic subtypes of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) and simian immunodeficiency virus (SIV), only in subtype C of HIV-1 is a genetically variant NF-κB binding site found at the core of the viral promoter in association with a subtype-specific Sp1III motif. How the subtype-associated variations in the core transcription factor binding sites (TFBS) influence gene expression from the viral promoter has not been examined previously. Using panels of infectious viral molecular clones, we demonstrate that subtype-specific NF-κB and Sp1III motifs have evolved for optimal gene expression, and neither of the motifs can be replaced by a corresponding TFBS variant. The variant NF-κB motif binds NF-κB with an affinity 2-fold higher than that of the generic NF-κB site. Importantly, in the context of an infectious virus, the subtype-specific Sp1III motif demonstrates a profound loss of function in association with the generic NF-κB motif. An additional substitution of the Sp1III motif fully restores viral replication, suggesting that the subtype C-specific Sp1III has evolved to function with the variant, but not generic, NF-κB motif. A change of only two base pairs in the central NF-κB motif completely suppresses viral transcription from the provirus and converts the promoter into heterochromatin refractory to tumor necrosis factor alpha (TNF-α) induction. The present work represents the first demonstration of functional incompatibility between an otherwise functional NF-κB motif and a unique Sp1 site in the context of an HIV-1 promoter. Our work provides important leads as to the evolution of the HIV-1 subtype C viral promoter with relevance for gene expression regulation and viral latency. IMPORTANCE Subtype-specific genetic variations provide a powerful tool to examine how these variations offer a replication advantage to specific viral subtypes, if any. Only in subtype C of HIV-1 are two genetically distinct transcription factor binding sites positioned at the most critical location of the viral promoter. Since a single promoter regulates viral gene expression, the promoter variations can play a critical role in determining the replication fitness of the viral strains. Our work for the first time provides a scientific explanation for the presence of a unique NF-κB binding motif in subtype C, a major HIV-1 genetic family responsible for half of the global HIV-1 infections. The results offer compelling evidence that the subtype C viral promoter not only is stronger but also is endowed with a qualitative gain-of-function advantage. The genetically variant NF-κB and the Sp1III motifs may be respond differently to specific cell signal pathways, and these mechanisms must be examined. PMID:27194770

Gene movement and genetic association with regional climate gradients in California valley oak (Quercus lobata Née) in the face of climate change

USGS Publications Warehouse

Sork, Victoria L.; Davis, Frank W.; Westfall, Robert; Flint, Alan L.; Ikegami, Makihiko; Wang, Hongfang; Grivet, Delphine

2010-01-01

Rapid climate change jeopardizes tree populations by shifting current climate zones. To avoid extinction, tree populations must tolerate, adapt, or migrate. Here we investigate geographic patterns of genetic variation in valley oak, Quercus lobata N??e, to assess how underlying genetic structure of populations might influence this species' ability to survive climate change. First, to understand how genetic lineages shape spatial genetic patterns, we examine historical patterns of colonization. Second, we examine the correlation between multivariate nuclear genetic variation and climatic variation. Third, to illustrate how geographic genetic variation could interact with regional patterns of 21st Century climate change, we produce region-specific bioclimatic distributions of valley oak using Maximum Entropy (MAXENT) models based on downscaled historical (1971-2000) and future (2070-2100) climate grids. Future climatologies are based on a moderate-high (A2) carbon emission scenario and two different global climate models. Chloroplast markers indicate historical range-wide connectivity via colonization, especially in the north. Multivariate nuclear genotypes show a strong association with climate variation that provides opportunity for local adaptation to the conditions within their climatic envelope. Comparison of regional current and projected patterns of climate suitability indicates that valley oaks grow in distinctly different climate conditions in different parts of their range. Our models predict widely different regional outcomes from local displacement of a few kilometres to hundreds of kilometres. We conclude that the relative importance of migration, adaptation, and tolerance are likely to vary widely for populations among regions, and that late 21st Century conditions could lead to regional extinctions. ?? 2010 Blackwell Publishing Ltd.

Gene movement and genetic association with regional climate gradients in California valley oak (Quercus lobata Née) in the face of climate change.

PubMed

Sork, Victoria L; Davis, Frank W; Westfall, Robert; Flint, Alan; Ikegami, Makihiko; Wang, Hongfang; Grivet, Delphine

2010-09-01

Rapid climate change jeopardizes tree populations by shifting current climate zones. To avoid extinction, tree populations must tolerate, adapt, or migrate. Here we investigate geographic patterns of genetic variation in valley oak, Quercus lobata Née, to assess how underlying genetic structure of populations might influence this species' ability to survive climate change. First, to understand how genetic lineages shape spatial genetic patterns, we examine historical patterns of colonization. Second, we examine the correlation between multivariate nuclear genetic variation and climatic variation. Third, to illustrate how geographic genetic variation could interact with regional patterns of 21st Century climate change, we produce region-specific bioclimatic distributions of valley oak using Maximum Entropy (MAXENT) models based on downscaled historical (1971-2000) and future (2070-2100) climate grids. Future climatologies are based on a moderate-high (A2) carbon emission scenario and two different global climate models. Chloroplast markers indicate historical range-wide connectivity via colonization, especially in the north. Multivariate nuclear genotypes show a strong association with climate variation that provides opportunity for local adaptation to the conditions within their climatic envelope. Comparison of regional current and projected patterns of climate suitability indicates that valley oaks grow in distinctly different climate conditions in different parts of their range. Our models predict widely different regional outcomes from local displacement of a few kilometres to hundreds of kilometres. We conclude that the relative importance of migration, adaptation, and tolerance are likely to vary widely for populations among regions, and that late 21st Century conditions could lead to regional extinctions.

The microgeographical patterns of morphological and molecular variation of a mixed ploidy population in the species complex Actinidia chinensis.

PubMed

Liu, Yifei; Li, Dawei; Yan, Ling; Huang, Hongwen

2015-01-01

Polyploidy and hybridization are thought to have significant impacts on both the evolution and diversification of the genus Actinidia, but the structure and patterns of morphology and molecular diversity relating to ploidy variation of wild Actinidia plants remain much less understood. Here, we examine the distribution of morphological variation and ploidy levels along geographic and environmental variables of a large mixed-ploidy population of the A. chinensis species complex. We then characterize the extent of both genetic and epigenetic diversity and differentiation exhibited between individuals of different ploidy levels. Our results showed that while there are three ploidy levels in this population, hexaploids were constituted the majority (70.3%). Individuals with different ploidy levels were microgeographically structured in relation to elevation and extent of niche disturbance. The morphological characters examined revealed clear difference between diploids and hexaploids, however tetraploids exhibited intermediate forms. Both genetic and epigenetic diversity were high but the differentiation among cytotypes was weak, suggesting extensive gene flow and/or shared ancestral variation occurred in this population even across ploidy levels. Epigenetic variation was clearly correlated with changes in altitudes, a trend of continuous genetic variation and gradual increase of epigenomic heterogeneities of individuals was also observed. Our results show that complex interactions between the locally microgeographical environment, ploidy and gene flow impact A. chinensis genetic and epigenetic variation. We posit that an increase in ploidy does not broaden the species habitat range, but rather permits A. chinensis adaptation to specific niches.

Genetic variation in Mycobacterium tuberculosis isolates from a London outbreak associated with isoniazid resistance.

PubMed

Satta, Giovanni; Witney, Adam A; Shorten, Robert J; Karlikowska, Magdalena; Lipman, Marc; McHugh, Timothy D

2016-08-16

The largest outbreak of isoniazid-resistant (INH-R) Mycobacterium tuberculosis in Western Europe is centred in North London, with over 400 cases diagnosed since 1995. In the current study, we evaluated the genetic variation in a subset of clinical samples from the outbreak with the hypothesis that these isolates have unique biological characteristics that have served to prolong the outbreak. Fitness assays, mutation rate estimation, and whole-genome sequencing were performed to test for selective advantage and compensatory mutations. This detailed analysis of the genetic variation of these INH-R samples suggests that this outbreak consists of successful, closely related, circulating strains with heterogeneous resistance profiles and little or no associated fitness cost or impact on their mutation rate. Specific deletions and SNPs could be a peculiar feature of these INH-R M. tuberculosis isolates, and could potentially explain their persistence over the years.

Nature, nurture and evolution of intra-species variation in mosquito arbovirus transmission competence.

PubMed

Tabachnick, Walter J

2013-01-11

Mosquitoes vary in their competence or ability to transmit arthropod-borne viruses (arboviruses). Many arboviruses cause disease in humans and animals. Identifying the environmental and genetic causes of variation in mosquito competence for arboviruses is one of the great challenges in public health. Progress identifying genetic (nature) and environmental (nurture) factors influencing mosquito competence for arboviruses is reviewed. There is great complexity in the various traits that comprise mosquito competence. The complex interactions between environmental and genetic factors controlling these traits and the factors shaping variation in Nature are largely unknown. The norms of reaction of specific genes influencing competence, their distributions in natural populations and the effects of genetic polymorphism on phenotypic variation need to be determined. Mechanisms influencing competence are not likely due to natural selection because of the direct effects of the arbovirus on mosquito fitness. More likely the traits for mosquito competence for arboviruses are the effects of adaptations for other functions of these competence mechanisms. Determining these other functions is essential to understand the evolution and distributions of competence for arboviruses. This information is needed to assess risk from mosquito-borne disease, predict new mosquito-arbovirus systems, and provide novel strategies to mitigate mosquito-borne arbovirus transmission.

A survey of the population genetic variation in the human kinome.

PubMed

Zhang, Wei; Catenacci, Daniel V T; Duan, Shiwei; Ratain, Mark J

2009-08-01

Protein kinases are key regulators of various biological processes, such as control of cell growth, metabolism, differentiation and apoptosis. Therefore, protein kinases have been an important class of targets for anticancer drugs. Health-related disparities such as differential drug response have been observed between human populations. A survey of the human kinases and their ligand genes for those containing population-specific genetic variants could provide new insights into the mechanisms of these health disparities and suggest novel targets for ethnicity-specific personalized medicine. Using the International HapMap Project genotypic data on single-nucleotide polymorphisms (SNPs), the protein kinase complement of the human genome (kinome) and some experimentally verified ligand genes were scanned for the existence of population-specific SNPs (eSNPs). In general, protein kinases were found to contain a much higher proportion of eSNPs than the whole genome background, indicating a stronger pressure for adaptation in individual populations. In contrast, the proportion of ligand genes containing eSNPs was not different from that of the whole genome background. Although with some important limitations, our results suggest that human kinases are more likely to be under recent positive selection than ligands. Our findings suggest that the health-related disparities associated with kinase signaling pathways are more likely to be driven by the genetic variation in the kinase genes than their cognate ligands. Illustrating the role of molecular evolution in the genetic variation of the human kinome could provide a promising route to understand the ethnic differences in cancer and facilitate the realization of ethnicity-based individualized medicine.

Functional annotation of HOT regions in the human genome: implications for human disease and cancer

PubMed Central

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-01-01

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy. PMID:26113264

Functional annotation of HOT regions in the human genome: implications for human disease and cancer.

PubMed

Li, Hao; Chen, Hebing; Liu, Feng; Ren, Chao; Wang, Shengqi; Bo, Xiaochen; Shu, Wenjie

2015-06-26

Advances in genome-wide association studies (GWAS) and large-scale sequencing studies have resulted in an impressive and growing list of disease- and trait-associated genetic variants. Most studies have emphasised the discovery of genetic variation in coding sequences, however, the noncoding regulatory effects responsible for human disease and cancer biology have been substantially understudied. To better characterise the cis-regulatory effects of noncoding variation, we performed a comprehensive analysis of the genetic variants in HOT (high-occupancy target) regions, which are considered to be one of the most intriguing findings of recent large-scale sequencing studies. We observed that GWAS variants that map to HOT regions undergo a substantial net decrease and illustrate development-specific localisation during haematopoiesis. Additionally, genetic risk variants are disproportionally enriched in HOT regions compared with LOT (low-occupancy target) regions in both disease-relevant and cancer cells. Importantly, this enrichment is biased toward disease- or cancer-specific cell types. Furthermore, we observed that cancer cells generally acquire cancer-specific HOT regions at oncogenes through diverse mechanisms of cancer pathogenesis. Collectively, our findings demonstrate the key roles of HOT regions in human disease and cancer and represent a critical step toward further understanding disease biology, diagnosis, and therapy.

Pain modality- and sex-specific effects of COMT genetic functional variants

PubMed Central

Belfer, Inna; Segall, Samantha K.; Lariviere, William R.; Smith, Shad B.; Dai, Feng; Slade, Gary G.; Rashid, Naim U.; Mogil, Jeffrey S.; Campbell, Claudia; Edwards, Robert; Liu, Qian; Bair, Eric; Maixner, William; Diatchenko, Luda

2013-01-01

The enzyme catechol-O-methyltransferase (COMT) metabolizes catecholamine neurotransmitters involved in a number of physiological functions including pain perception. Both human and mouse COMT genes possess functional polymorphisms contributing to inter-individual variability in pain phenotypes such as sensitivity to noxious stimuli, severity of clinical pain and response to pain treatment. In this study, we found that the effects of Comt functional variation in mice are modality-specific. Spontaneous inflammatory nociception and thermal nociception behaviors were correlated the most with the presence of the B2 SINE transposon insertion residing in the 3’UTR mRNA region. Similarly, in humans, COMT functional haplotypes were associated with thermal pain perception and with capsaicin-induced pain. Furthermore, COMT genetic variations contributed to pain behaviors in mice and pain ratings in humans in a sex-specific manner. The ancestral Comt variant, without a B2 SINE insertion, was more strongly associated with sensitivity to capsaicin in female versus male mice. In humans, the haplotype coding for low COMT activity increased capsaicin-induced pain perception in women, but not men. These findings reemphasize the fundamental contribution of COMT to pain processes, and provide a fine-grained resolution of this contribution at the genetic level that can be used to guide future studies in the area of pain genetics. PMID:23701723

Trait Variation in Yeast Is Defined by Population History

PubMed Central

Warringer, Jonas; Zörgö, Enikö; Cubillos, Francisco A.; Zia, Amin; Gjuvsland, Arne; Simpson, Jared T.; Forsmark, Annabelle; Durbin, Richard; Omholt, Stig W.; Louis, Edward J.; Liti, Gianni; Moses, Alan; Blomberg, Anders

2011-01-01

A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism. PMID:21698134

Trait variation in yeast is defined by population history.

PubMed

Warringer, Jonas; Zörgö, Enikö; Cubillos, Francisco A; Zia, Amin; Gjuvsland, Arne; Simpson, Jared T; Forsmark, Annabelle; Durbin, Richard; Omholt, Stig W; Louis, Edward J; Liti, Gianni; Moses, Alan; Blomberg, Anders

2011-06-01

A fundamental goal in biology is to achieve a mechanistic understanding of how and to what extent ecological variation imposes selection for distinct traits and favors the fixation of specific genetic variants. Key to such an understanding is the detailed mapping of the natural genomic and phenomic space and a bridging of the gap that separates these worlds. Here we chart a high-resolution map of natural trait variation in one of the most important genetic model organisms, the budding yeast Saccharomyces cerevisiae, and its closest wild relatives and trace the genetic basis and timing of major phenotype changing events in its recent history. We show that natural trait variation in S. cerevisiae exceeds that of its relatives, despite limited genetic variation, and follows the population history rather than the source environment. In particular, the West African population is phenotypically unique, with an extreme abundance of low-performance alleles, notably a premature translational termination signal in GAL3 that cause inability to utilize galactose. Our observations suggest that many S. cerevisiae traits may be the consequence of genetic drift rather than selection, in line with the assumption that natural yeast lineages are remnants of recent population bottlenecks. Disconcertingly, the universal type strain S288C was found to be highly atypical, highlighting the danger of extrapolating gene-trait connections obtained in mosaic, lab-domesticated lineages to the species as a whole. Overall, this study represents a step towards an in-depth understanding of the causal relationship between co-variation in ecology, selection pressure, natural traits, molecular mechanism, and alleles in a key model organism.

Genetic variation in serotonin function impacts on altruistic punishment in the ultimatum game: A longitudinal approach.

PubMed

Gärtner, Anne; Strobel, Alexander; Reif, Andreas; Lesch, Klaus-Peter; Enge, Sören

2018-05-30

Growing evidence demonstrates that the serotonin system influences punishment behavior in social decision-making and that individual differences in the propensity to punish are, at least in part, due to genetic variation. However, the specific genes and their mechanisms by which they influence punishment behavior are not yet fully characterized. Here, we examined whether serotonin system-related gene variation impacts on altruistic punishment in the ultimatum game by using a longitudinal approach with three time points, covering a time frame up to four months in young adults (N = 106). Specifically, we investigated additive effects of 5-HTTLPR and TPH2 G-703T genotypes by using a composite score. This composite score was significantly associated with altruistic punishment, with individuals carrying both the S-allele and the G-allele demonstrating less punishment behavior. The results suggest that serotonin system-related gene variation contributes to individual differences in altruistic punishment. Furthermore, comparably high test-retest correlations suggest that punishment behavior in the ultimatum game represents a relatively stable, trait-like behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

Polymorphisms in the Wilms Tumor Gene Are Associated With Interindividual Variations in Rubella Virus-Specific Cellular Immunity After Measles-Mumps-Rubella II Vaccination.

PubMed

Voigt, Emily A; Haralambieva, Iana H; Larrabee, Beth L; Kennedy, Richard B; Ovsyannikova, Inna G; Schaid, Daniel J; Poland, Gregory A

2018-01-30

Rubella vaccination induces widely variable immune responses in vaccine recipients. While rubella vaccination is effective at inducing immunity to rubella infection in most subjects, up to 5% of individuals do not achieve or maintain long-term protective immunity. To expand upon our previous work identifying genetic polymorphisms that are associated with these interindividual differences in humoral immunity to rubella virus, we performed a genome-wide association study in a large cohort of 1843 subjects to discover single-nucleotide polymorphisms (SNPs) associated with rubella virus-specific cellular immune responses. We identified SNPs in the Wilms tumor protein gene (WT1) that were significantly associated (P < 5 × 10-8) with interindividual variations in rubella-specific interleukin 6 secretion from subjects' peripheral blood mononuclear cells postvaccination. No SNPs were found to be significantly associated with variations in rubella-specific interferon-γ secretion. Our findings demonstrate that genetic polymorphisms in the WT1 gene in subjects of European ancestry are associated with interindividual differences in rubella virus-specific cellular immunity after measles-mumps-rubella II vaccination. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The genetics of addiction—a translational perspective

PubMed Central

Agrawal, A; Verweij, K J H; Gillespie, N A; Heath, A C; Lessov-Schlaggar, C N; Martin, N G; Nelson, E C; Slutske, W S; Whitfield, J B; Lynskey, M T

2012-01-01

Addictions are serious and common psychiatric disorders, and are among the leading contributors to preventable death. This selective review outlines and highlights the need for a multi-method translational approach to genetic studies of these important conditions, including both licit (alcohol, nicotine) and illicit (cannabis, cocaine, opiates) drug addictions and the behavioral addiction of disordered gambling. First, we review existing knowledge from twin studies that indicates both the substantial heritability of substance-specific addictions and the genetic overlap across addiction to different substances. Next, we discuss the limited number of candidate genes which have shown consistent replication, and the implications of emerging genomewide association findings for the genetic architecture of addictions. Finally, we review the utility of extensions to existing methods such as novel phenotyping, including the use of endophenotypes, biomarkers and neuroimaging outcomes; emerging methods for identifying alternative sources of genetic variation and accompanying statistical methodologies to interpret them; the role of gene–environment interplay; and importantly, the potential role of genetic variation in suggesting new alternatives for treatment of addictions. PMID:22806211

Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases.

PubMed

Bueno, Anibal; Rodríguez-López, Rocío; Reyes-Palomares, Armando; Rojano, Elena; Corpas, Manuel; Nevado, Julián; Lapunzina, Pablo; Sánchez-Jiménez, Francisca; Ranea, Juan A G

2018-06-26

Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8-9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype-phenotype relationships. We aimed to improve the identification of statistically consistent genotype-phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype-patient-genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes.

Direct testing for allele-specific expression differences between conditions

USDA-ARS?s Scientific Manuscript database

Genetic differences in cis regulatory regions contribute to the phenotypic variation observed in natural and human populations, including beneficial, potentially adaptive, traits as well as disease states. The two alleles in a diploid cell can differ in their allele-specific expression leading to al...

Ecological and population genetics of locally rare plants: A review

Treesearch

Simon A. Lei

2001-01-01

Plant species with limited dispersal ability, narrow geographical and physiological tolerance ranges, as well as with specific habitat and ecological requirements are likely to be rare. Small and isolated populations and species contain low levels of within-population genetic variation in many plant species. The gene pool of plants is a product of phenotype-environment...

Oxytocin receptor gene polymorphism modulates the effects of social support on heart rate variability

PubMed Central

Kanthak, Magdalena K.; Chen, Frances S.; Kumsta, Robert; Hill, LaBarron K.; Thayer, Julian F.; Heinrichs, Markus

2017-01-01

A large body of empirical research has demonstrated stress-buffering effects of social support. However, recent studies suggest that genetic variation of the oxytocin system (specifically, a common single nucleotide polymorphism, rs53576, of the oxytocin receptor gene) modulates the efficacy of social support. The timing and neurobiological basis of this genetic modulation were investigated using a standardized, laboratory-based psychological stress procedure (Trier Social Stress Test for Groups, TSST-G). To index potential stress buffering effects of social support mediated by the oxytocin system, heart rate variability (HRV) was obtained before and during the TSST-G from 40 healthy participants. Results indicate that social support is associated with higher HRV only in G allele carriers. Specifically, social support increased heart rate variability during direct social interaction and only in individuals with at least one copy of the G allele of rs53576. These findings support the idea that the stress-attenuating effects of social support are modulated by genetic variation of the oxytocin system. PMID:26903384

The heritability of aptitude and exceptional talent across different domains in adolescents and young adults.

PubMed

Vinkhuyzen, Anna A E; van der Sluis, Sophie; Posthuma, Danielle; Boomsma, Dorret I

2009-07-01

The origin of individual differences in aptitude, defined as a domain-specific skill within the normal ability range, and talent, defined as a domain specific skill of exceptional quality, is under debate. The nature of the variation in aptitudes and exceptional talents across different domains was investigated in a population based twin sample. Self-report data from 1,685 twin pairs (12-24 years) were analyzed for Music, Arts, Writing, Language, Chess, Mathematics, Sports, Memory, and Knowledge. The influence of shared environment was small for both aptitude and talent. Additive and non-additive genetic effects explained the major part of the substantial familial clustering in the aptitude measures with heritability estimates ranging between .32 and .71. Heritability estimates for talents were higher and ranged between .50 and .92. In general, the genetic architecture for aptitude and talent was similar in men and women. Genetic factors contribute to a large extent to variation in aptitude and talent across different domains of intellectual, creative, and sports abilities.

Genetic and environmental effects on body mass index from infancy to the onset of adulthood: an individual-based pooled analysis of 45 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) study.

PubMed

Silventoinen, Karri; Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Honda, Chika; Hjelmborg, Jacob vB; Möller, Sören; Ooki, Syuichi; Aaltonen, Sari; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J; Jang, Kerry L; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P; Huibregtse, Brooke M; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth Jf; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S Alexandra; Klump, Kelly L; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A; Bartels, Meike; van Beijsterveldt, Toos Cem; Craig, Jeffrey M; Saffery, Richard; Freitas, Duarte L; Maia, José Antonio; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Chong, Youngsook; Swan, Gary E; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire Ma; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K Paige; Tucker-Drob, Elliot M; Öncel, Sevgi Y; Aliev, Fazil; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A; Tuvblad, Catherine; Duncan, Glen E; Buchwald, Dedra; Willemsen, Gonneke; Rasmussen, Finn; Goldberg, Jack H; Sørensen, Thorkild Ia; Boomsma, Dorret I; Kaprio, Jaakko

2016-08-01

Both genetic and environmental factors are known to affect body mass index (BMI), but detailed understanding of how their effects differ during childhood and adolescence is lacking. We analyzed the genetic and environmental contributions to BMI variation from infancy to early adulthood and the ways they differ by sex and geographic regions representing high (North America and Australia), moderate (Europe), and low levels (East Asia) of obesogenic environments. Data were available for 87,782 complete twin pairs from 0.5 to 19.5 y of age from 45 cohorts. Analyses were based on 383,092 BMI measurements. Variation in BMI was decomposed into genetic and environmental components through genetic structural equation modeling. The variance of BMI increased from 5 y of age along with increasing mean BMI. The proportion of BMI variation explained by additive genetic factors was lowest at 4 y of age in boys (a(2) = 0.42) and girls (a(2) = 0.41) and then generally increased to 0.75 in both sexes at 19 y of age. This was because of a stronger influence of environmental factors shared by co-twins in midchildhood. After 15 y of age, the effect of shared environment was not observed. The sex-specific expression of genetic factors was seen in infancy but was most prominent at 13 y of age and older. The variance of BMI was highest in North America and Australia and lowest in East Asia, but the relative proportion of genetic variation to total variation remained roughly similar across different regions. Environmental factors shared by co-twins affect BMI in childhood, but little evidence for their contribution was found in late adolescence. Our results suggest that genetic factors play a major role in the variation of BMI in adolescence among populations of different ethnicities exposed to different environmental factors related to obesity. © 2016 American Society for Nutrition.

Racial disparities: disruptive genes in prostate carcinogenesis.

PubMed

Singh, Savita; Plaga, Alexis; Shukla, Girish C

2017-06-01

Population specific studies in prostate cancer (PCa) reveal a unique heterogeneous etiology. Various factors, such as genetics, environment and dietary regimen seems to determine disease progression, therapeutic resistance and rate of mortality. Enormous disparity documented in disease incidences, aggressiveness and mortality in PCa among AAs (African Americans) and CAs (Caucasian Americans) is attributed to the variations in genetics, epigenetics and their association with metabolism. Scientific and clinical evidences have revealed the influence of variations in Androgen Receptor (AR), RNAse L, macrophage scavenger receptor 1 ( MRS1 ), androgen metabolism by cytochrome P450 3A4, differential regulation of microRNAs, epigenetic alterations and diet in racial disparity in PCa incidences and mortality. Concerted efforts are needed to identify race specific prognostic markers and treatment regimen for a better management of the disease.

Genetic identity affects performance of species in grasslands of different plant diversity: an experiment with Lolium perenne cultivars.

PubMed

Roscher, Christiane; Schumacher, Jens; Weisser, Wolfgang W; Schulze, Ernst-Detlef

2008-07-01

Recent biodiversity research has focused on ecosystem processes, but less is known about responses of populations of individual plant species to changing community diversity and implications of genetic variation within species. To address these issues, effects of plant community diversity on the performance of different cultivars of Lolium perenne were analysed. Populations of 15 genetic cultivars of Lolium perenne were established in experimental grasslands varying in richness of species (from 1 to 60) and functional groups (from 1 to 4). Population sizes, mean size of individual plants, biomass of individual shoots and seed production were measured in the first and second growing season after establishment. Population sizes of all cultivars decreased with increasing community species richness. Plant individuals formed fewer shoots with a lower shoot mass in more species-rich plant communities. A large proportion of variation in plant size and relative population growth was attributable to effects of community species and functional group richness, but the inclusion of cultivar identity explained additional 4-7 % of variation. Cultivar identity explained most variation (28-51 %) at the shoot level (biomass of individual tillers and reproductive shoots, seed production, heading stage). Coefficients of variation of the measured variables across plant communities were larger in cultivars with a lower average performance, indicating that this variation was predominantly due to passive growth reductions and not a consequence of larger adaptive plastic responses. No single cultivar performed best in all communities. The decreasing performance of Lolium perenne in plant communities of increasing species richness suggests a regulation of competitive interactions by species diversity. Genetic variation within species provides a base for larger phenotypic variation and may affect competitive ability. However, heterogeneous biotic environments (= plant communities of different species composition) are important for the maintenance of intra-specific genetic variation.

Developmental origins of novel gut morphology in frogs

PubMed Central

Bloom, Stephanie; Ledon-Rettig, Cris; Infante, Carlos; Everly, Anne; Hanken, James; Nascone-Yoder, Nanette

2013-01-01

SUMMARY Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation. PMID:23607305

Whole-genome comparison of meticillin-resistant Staphylococcus aureus CC22 SCCmecIV from people and their in-contact pets.

PubMed

Loeffler, Anette; McCarthy, Alex; Lloyd, David H; Musilová, Eva; Pfeiffer, Dirk U; Lindsay, Jodi A

2013-10-01

Meticillin-resistant Staphylococcus aureus (MRSA) infections remain important medical and veterinary challenges. The MRSA isolated from dogs and cats typically belong to dominant hospital-associated clones, in the UK mostly EMRSA-15 (CC22 SCCmecIV), suggesting original human-to-animal transmission. Nevertheless, little is known about host-specific genetic variation within the same S. aureus lineage. To identify host-specific variation amongst MRSA CC22 SCCmecIV by comparing isolates from pets with those from in-contact humans using whole-genome microarray. Six pairs of MRSA CC22 SCCmecIV from human carriers (owners and veterinary staff) and their respective infected in-contact pets were compared using a 62-strain whole-genome S. aureus microarray (SAM-62). The presence of putative host-specific genes was subsequently determined in a larger number of human (n = 47) and pet isolates (n = 93) by PCR screening. Variation in mobile genetic elements (MGEs) occurred frequently and appeared largely independent of host and in-contact pair. A plasmid (SAP078A) encoding heavy-metal resistance genes (arsR, arsA, cadA, cadC, mco and copB) was found in three of six human and none of six animal isolates. However, only two of four resistance genes were associated with human hosts (P = 0.015 for arsA and cadA). The variation found amongst MGEs highlights that genetic adaptation in MRSA continues. However, host-specific MGEs were not detected, which supports the hypothesis that pets may not be natural hosts of MRSA CC22 and emphasizes that rigorous hygiene measures are critical to prevent contamination and infection of dogs and cats. The host specificity of individual heavy-metal resistance genes warrants further investigation into different selection pressures in humans and animals. © 2013 ESVD and ACVD.

Local topography shapes fine-scale spatial genetic structure in the Arkansas Valley evening primrose, Oenothera harringtonii (Onagraceae).

PubMed

Rhodes, Matthew K; Fant, Jeremie B; Skogen, Krissa A

2014-01-01

Identifying factors that shape the spatial distribution of genetic variation is crucial to understanding many population- and landscape-level processes. In this study, we explore fine-scale spatial genetic structure in Oenothera harringtonii (Onagraceae), an insect-pollinated, gravity-dispersed herb endemic to the grasslands of south-central and southeastern Colorado, USA. We genotyped 315 individuals with 11 microsatellite markers and utilized a combination of spatial autocorrelation analyses and landscape genetic models to relate life history traits and landscape features to dispersal processes. Spatial genetic structure was consistent with theoretical expectations of isolation by distance, but this pattern was weak (Sp = 0.00374). Anisotropic analyses indicated that spatial genetic structure was markedly directional, in this case consistent with increased dispersal along prominent slopes. Landscape genetic models subsequently confirmed that spatial genetic variation was significantly influenced by local topographic heterogeneity, specifically that geographic distance, elevation and aspect were important predictors of spatial genetic structure. Among these variables, geographic distance was ~68% more important than elevation in describing spatial genetic variation, and elevation was ~42% more important than aspect after removing the effect of geographic distance. From these results, we infer a mechanism of hydrochorous seed dispersal along major drainages aided by seasonal monsoon rains. Our findings suggest that landscape features may shape microevolutionary processes at much finer spatial scales than typically considered, and stress the importance of considering how particular dispersal vectors are influenced by their environmental context. © The American Genetic Association 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Transcript Isoform Variation Associated with Cytosine Modification in Human Lymphoblastoid Cell Lines.

PubMed

Zhang, Xu; Zhang, Wei

2016-06-01

Cytosine modification on DNA is variable among individuals, which could correlate with gene expression variation. The effect of cytosine modification on interindividual transcript isoform variation (TIV), however, remains unclear. In this study, we assessed the extent of cytosine modification-specific TIV in lymphoblastoid cell lines (LCLs) derived from unrelated individuals of European and African descent. Our study detected cytosine modification-specific TIVs for 17% of the analyzed genes at a 5% false discovery rate. Forty-five percent of the TIV-associated cytosine modifications correlated with the overall gene expression levels as well, with the corresponding CpG sites overrepresented in transcript initiation sites, transcription factor binding sites, and distinct histone modification peaks, suggesting that alternative isoform transcription underlies the TIVs. Our analysis also revealed 33% of the TIV-associated cytosine modifications that affected specific exons, with the corresponding CpG sites overrepresented in exon/intron junctions, splicing branching points, and transcript termination sites, implying that the TIVs are attributable to alternative splicing or transcription termination. Genetic and epigenetic regulation of TIV shared target preference but exerted independent effects on 61% of the common exon targets. Cytosine modification-specific TIVs detected from LCLs were differentially enriched in those detected from various tissues in The Cancer Genome Atlas, indicating their developmental dependency. Genes containing cytosine modification-specific TIVs were enriched in pathways of cancers and metabolic disorders. Our study demonstrated a prominent effect of cytosine modification variation on the transcript isoform spectrum over gross transcript abundance and revealed epigenetic contributions to diseases that were mediated through cytosine modification-specific TIV. Copyright © 2016 by the Genetics Society of America.

Hsp90 prevents phenotypic variation by suppressing the mutagenic activity of transposons.

PubMed

Specchia, Valeria; Piacentini, Lucia; Tritto, Patrizia; Fanti, Laura; D'Alessandro, Rosalba; Palumbo, Gioacchino; Pimpinelli, Sergio; Bozzetti, Maria P

2010-02-04

The canalization concept describes the resistance of a developmental process to phenotypic variation, regardless of genetic and environmental perturbations, owing to the existence of buffering mechanisms. Severe perturbations, which overcome such buffering mechanisms, produce altered phenotypes that can be heritable and can themselves be canalized by a genetic assimilation process. An important implication of this concept is that the buffering mechanism could be genetically controlled. Recent studies on Hsp90, a protein involved in several cellular processes and development pathways, indicate that it is a possible molecular mechanism for canalization and genetic assimilation. In both flies and plants, mutations in the Hsp90-encoding gene induce a wide range of phenotypic abnormalities, which have been interpreted as an increased sensitivity of different developmental pathways to hidden genetic variability. Thus, Hsp90 chaperone machinery may be an evolutionarily conserved buffering mechanism of phenotypic variance, which provides the genetic material for natural selection. Here we offer an additional, perhaps alternative, explanation for proposals of a concrete mechanism underlying canalization. We show that, in Drosophila, functional alterations of Hsp90 affect the Piwi-interacting RNA (piRNA; a class of germ-line-specific small RNAs) silencing mechanism leading to transposon activation and the induction of morphological mutants. This indicates that Hsp90 mutations can generate new variation by transposon-mediated 'canonical' mutagenesis.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

PubMed Central

2010-01-01

Background Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Results Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Conclusion Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. PMID:20707912

Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges

PubMed Central

2018-01-01

Schizophrenia (SZ) is a heritable brain disease originating from a complex interaction of genetic and environmental factors. The genes underpinning the neurobiology of SZ are largely unknown but recent data suggest strong evidence for genetic variations, such as single nucleotide polymorphisms, making the brain vulnerable to the risk of SZ. Structural and functional brain mapping of these genetic variations are essential for the development of agents and tools for better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging methods in combination with genetic analysis have been increasingly used for almost 20 years. So-called imaging genetics, the opportunities of this approach along with its limitations for SZ research will be outlined in this invited paper. While the problems such as reproducibility, genetic effect size, specificity and sensitivity exist, opportunities such as multivariate analysis, development of multisite consortia for large-scale data collection, emergence of non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely to contribute to a rapid progress for gene discovery besides to gene validation studies that are related to SZ. PMID:29324666

Transposable elements generate population-specific insertional patterns and allelic variation in genes of wild emmer wheat (Triticum turgidum ssp. dicoccoides).

PubMed

Domb, Katherine; Keidar, Danielle; Yaakov, Beery; Khasdan, Vadim; Kashkush, Khalil

2017-10-27

Natural populations of the tetraploid wild emmer wheat (genome AABB) were previously shown to demonstrate eco-geographically structured genetic and epigenetic diversity. Transposable elements (TEs) might make up a significant part of the genetic and epigenetic variation between individuals and populations because they comprise over 80% of the wild emmer wheat genome. In this study, we performed detailed analyses to assess the dynamics of transposable elements in 50 accessions of wild emmer wheat collected from 5 geographically isolated sites. The analyses included: the copy number variation of TEs among accessions in the five populations, population-unique insertional patterns, and the impact of population-unique/specific TE insertions on structure and expression of genes. We assessed the copy numbers of 12 TE families using real-time quantitative PCR, and found significant copy number variation (CNV) in the 50 wild emmer wheat accessions, in a population-specific manner. In some cases, the CNV difference reached up to 6-fold. However, the CNV was TE-specific, namely some TE families showed higher copy numbers in one or more populations, and other TE families showed lower copy numbers in the same population(s). Furthermore, we assessed the insertional patterns of 6 TE families using transposon display (TD), and observed significant population-specific insertional patterns. The polymorphism levels of TE-insertional patterns reached 92% among all wild emmer wheat accessions, in some cases. In addition, we observed population-specific/unique TE insertions, some of which were located within or close to protein-coding genes, creating allelic variations in a population-specific manner. We also showed that those genes are differentially expressed in wild emmer wheat. For the first time, this study shows that TEs proliferate in wild emmer wheat in a population-specific manner, creating new alleles of genes, which contribute to the divergent evolution of homeologous genes from the A and B subgenomes.

GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics.

PubMed

Ledda, Mirko; Kutalik, Zoltán; Souza Destito, Maria C; Souza, Milena M; Cirillo, Cintia A; Zamboni, Amabilene; Martin, Nathalie; Morya, Edgard; Sameshima, Koichi; Beckmann, Jacques S; le Coutre, Johannes; Bergmann, Sven; Genick, Ulrich K

2014-01-01

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10(-13), r(2) = 8.9%, β = -0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with-but is statistically distinct from-the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10(-37), r(2) = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception.

Consensus pan-genome assembly of the specialised wine bacterium Oenococcus oeni.

PubMed

Sternes, Peter R; Borneman, Anthony R

2016-04-27

Oenococcus oeni is a lactic acid bacterium that is specialised for growth in the ecological niche of wine, where it is noted for its ability to perform the secondary, malolactic fermentation that is often required for many types of wine. Expanding the understanding of strain-dependent genetic variations in its small and streamlined genome is important for realising its full potential in industrial fermentation processes. Whole genome comparison was performed on 191 strains of O. oeni; from this rich source of genomic information consensus pan-genome assemblies of the invariant (core) and variable (flexible) regions of this organism were established. Genetic variation in amino acid biosynthesis and sugar transport and utilisation was found to be common between strains. Furthermore, we characterised previously-unreported intra-specific genetic variations in the natural competence of this microbe. By assembling a consensus pan-genome from a large number of strains, this study provides a tool for researchers to readily compare protein-coding genes across strains and infer functional relationships between genes in conserved syntenic regions. This establishes a foundation for further genetic, and thus phenotypic, research of this industrially-important species.

Meiotic recombination hotspots - a comparative view.

PubMed

Choi, Kyuha; Henderson, Ian R

2015-07-01

During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Widespread covariation of early environmental exposures and trait-associated polygenic variation.

PubMed

Krapohl, E; Hannigan, L J; Pingault, J-B; Patel, H; Kadeva, N; Curtis, C; Breen, G; Newhouse, S J; Eley, T C; O'Reilly, P F; Plomin, R

2017-10-31

Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample ( n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age ( R 2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding ( R 2 = 0.021; P = 7e-30), maternal smoking during pregnancy ( R 2 = 0.008; P = 5e-13), parental smacking ( R 2 = 0.01; P = 4e-15), household income ( R 2 = 0.032; P = 1e-22), watching television ( R 2 = 0.034; P = 5e-47), and maternal education ( R 2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.

Global and disease-associated genetic variation in the human Fanconi anemia gene family

PubMed Central

Rogers, Kai J.; Fu, Wenqing; Akey, Joshua M.; Monnat, Raymond J.

2014-01-01

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57 240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. PMID:25104853

An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.

PubMed

Bidwell, L C; McGeary, J E; Gray, J C; Palmer, R H C; Knopik, V S; MacKillop, J

2015-11-01

Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-wide association study reveals sex-specific selection signals against autosomal nucleotide variants.

PubMed

Ryu, Dongchan; Ryu, Jihye; Lee, Chaeyoung

2016-05-01

A genome-wide association study (GWAS) was conducted to examine genetic associations of common autosomal nucleotide variants with sex in a Korean population with 4183 males and 4659 females. Nine genetic association signals were identified in four intragenic and five intergenic regions (P<5 × 10(-8)). Further analysis with an independent data set confirmed two intragenic association signals in the genes encoding protein phosphatase 1, regulatory subunit 12B (PPP1R12B, intron 12, rs1819043) and dynein, axonemal, heavy chain 11 (DNAH11, intron 61, rs10255013), which are directly involved in the reproductive system. This study revealed autosomal genetic variants associated with sex ratio by GWAS for the first time. This implies that genetic variants in proximity to the association signals may influence sex-specific selection and contribute to sex ratio variation. Further studies are required to reveal the mechanisms underlying sex-specific selection.

Biodiversity of mannose-specific adhesion in Lactobacillus plantarum revisited: strain-specific domain composition of the mannose-adhesin.

PubMed

Gross, G; Snel, J; Boekhorst, J; Smits, M A; Kleerebezem, M

2010-03-01

Recently, we have identified the mannose-specific adhesin encoding gene (msa) of Lactobacillus plantarum. In the current study, structure and function of this potentially probiotic effector gene were further investigated, exploring genetic diversity of msa in L. plantarum in relation to mannose adhesion capacity. The results demonstrate that there is considerable variation in quantitative in vitro mannose adhesion capacity, which is paralleled by msa gene sequence variation. The msa genes of different L. plantarum strains encode proteins with variable domain composition. Construction of L. plantarum 299v mutant strains revealed that the msa gene product is the key-protein for mannose adhesion, also in a strain with high mannose adhering capacity. However, no straightforward correlation between adhesion capacity and domain composition of Msa in L. plantarum could be identified. Nevertheless, differences in Msa sequences in combination with variable genetic background of specific bacterial strains appears to determine mannose adhesion capacity and potentially affects probiotic properties. These findings exemplify the strain-specificity of probiotic characteristics and illustrate the need for careful and molecular selection of new candidate probiotics.

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem[OPEN

PubMed Central

Eshbaugh, Robert; Chen, Fang; Atwell, Susana

2017-01-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana-Botrytis cinerea pathosystem to test how the host’s defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1, individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea. This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. PMID:29042403

Genetic variation for pseudo-self-compatibility in self-incompatible populations of Leavenworthia alabamica (Brassicaceae).

PubMed

Baldwin, Sarah J; Schoen, Daniel J

2017-01-01

Self-incompatibility (SI) promotes outcrossing, but transitions to self-compatibility (SC) are frequent. Population genetic theory describing the breakdown of SI to SC suggests that, under most conditions, populations should be composed of either SI or SC individuals. Under a narrow range of conditions, theory suggests that SI may persist alongside reduced expression of SI (pseudo-SI, PSI) in mixed-mating populations. We studied genetic variation for PSI segregating in four SI populations of Leavenworthia alabamica by measurement of the heritability of pollen tube number after self-pollination. We tested for the role of the S-locus in this variation by sequencing seven S-alleles from plants with high pseudo-SC (PSC) and testing for the co-segregation of these alleles with PSC. We found a continuous distribution of PSC in all populations and 90% of plants exhibited PSC. The heritability ranged from 0.39 to 0.57. All seven S-alleles from plants with high PSC exhibited trans-specific polymorphism, and no stop codons were observed within the c. 600-bp region sequenced. One of these S-alleles was directly associated with the inheritance of PSC. We conclude that heritable variation in PSC is largely a result of genetic variation in the signaling cascade downstream of the S-locus reaction, together with the presence of one leaky S-allele. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Plastic Transcriptomes Stabilize Immunity to Pathogen Diversity: The Jasmonic Acid and Salicylic Acid Networks within the Arabidopsis/Botrytis Pathosystem.

PubMed

Zhang, Wei; Corwin, Jason A; Copeland, Daniel; Feusier, Julie; Eshbaugh, Robert; Chen, Fang; Atwell, Susana; Kliebenstein, Daniel J

2017-11-01

To respond to pathogen attack, selection and associated evolution has led to the creation of plant immune system that are a highly effective and inducible defense system. Central to this system are the plant defense hormones jasmonic acid (JA) and salicylic acid (SA) and crosstalk between the two, which may play an important role in defense responses to specific pathogens or even genotypes. Here, we used the Arabidopsis thaliana - Botrytis cinerea pathosystem to test how the host's defense system functions against genetic variation in a pathogen. We measured defense-related phenotypes and transcriptomic responses in Arabidopsis wild-type Col-0 and JA- and SA-signaling mutants, coi1-1 and npr1-1 , individually challenged with 96 diverse B. cinerea isolates. Those data showed genetic variation in the pathogen influences on all components within the plant defense system at the transcriptional level. We identified four gene coexpression networks and two vectors of defense variation triggered by genetic variation in B. cinerea This showed that the JA and SA signaling pathways functioned to constrain/canalize the range of virulence in the pathogen population, but the underlying transcriptomic response was highly plastic. These data showed that plants utilize major defense hormone pathways to buffer disease resistance, but not the metabolic or transcriptional responses to genetic variation within a pathogen. © 2017 American Society of Plant Biologists. All rights reserved.

Landscape genetics of Schistocephalus solidus parasites in threespine stickleback (Gasterosteus aculeatus) from Alaska.

PubMed

Sprehn, C Grace; Blum, Michael J; Quinn, Thomas P; Heins, David C

2015-01-01

The nature of gene flow in parasites with complex life cycles is poorly understood, particularly when intermediate and definitive hosts have contrasting movement potential. We examined whether the fine-scale population genetic structure of the diphyllobothriidean cestode Schistocephalus solidus reflects the habits of intermediate threespine stickleback hosts or those of its definitive hosts, semi-aquatic piscivorous birds, to better understand complex host-parasite interactions. Seventeen lakes in the Cook Inlet region of south-central Alaska were sampled, including ten in the Matanuska-Susitna Valley, five on the Kenai Peninsula, and two in the Bristol Bay drainage. We analyzed sequence variation across a 759 bp region of the mitochondrial DNA (mtDNA) cytochrome oxidase I region for 1,026 S. solidus individuals sampled from 2009-2012. We also analyzed allelic variation at 8 microsatellite loci for 1,243 individuals. Analysis of mtDNA haplotype and microsatellite genotype variation recovered evidence of significant population genetic structure within S. solidus. Host, location, and year were factors in structuring observed genetic variation. Pairwise measures revealed significant differentiation among lakes, including a pattern of isolation-by-distance. Bayesian analysis identified three distinct genotypic clusters in the study region, little admixture within hosts and lakes, and a shift in genotype frequencies over time. Evidence of fine-scale population structure in S. solidus indicates that movement of its vagile, definitive avian hosts has less influence on gene flow than expected based solely on movement potential. Observed patterns of genetic variation may reflect genetic drift, behaviors of definitive hosts that constrain dispersal, life history of intermediate hosts, and adaptive specificity of S. solidus to intermediate host genotype.

Inbreeding Depression and Male Survivorship in Drosophila: Implications for Senescence Theory

PubMed Central

Swindell, William R.; Bouzat, Juan L.

2006-01-01

The extent to which inbreeding depression affects longevity and patterns of survivorship is an important issue from several research perspectives, including evolutionary biology, conservation biology, and the genetic analysis of quantitative traits. However, few previous inbreeding depression studies have considered longevity as a focal life-history trait. We maintained laboratory populations of Drosophila melanogaster at census population sizes of 2 and 10 male-female pairs for up to 66 generations and performed repeated assays of male survivorship throughout this time period. On average, significant levels of inbreeding depression were observed for median life span and age-specific mortality. For age-specific mortality, the severity of inbreeding depression increased over the life span. We found that a baseline inbreeding load of 0.307 lethal equivalents per gamete affected age-specific mortality, and that this value increased at a rate of 0.046 per day of the life span. With respect to some survivorship parameters, the differentiation of lineages was nonlinear with respect to the inbreeding coefficient, which suggested that nonadditive genetic variation contributed to variation among lineages. These findings provide insights into the genetic basis of longevity as a quantitative trait and have implications regarding the mutation-accumulation evolutionary explanation of senescence. PMID:16204222

Ancestry-Specific Methylation Patterns in Admixed Offspring from an Experimental Coyote and Gray Wolf Cross.

PubMed

vonHoldt, Bridgett; Heppenheimer, Elizabeth; Petrenko, Vladimir; Croonquist, Paula; Rutledge, Linda Y

2017-06-01

Reduced fitness of admixed individuals is typically attributed to genetic incompatibilities. Although mismatched genomes can lead to fitness changes, in some cases the reduction in hybrid fitness is subtle. The potential role of transcriptional regulation in admixed genomes could provide a mechanistic explanation for these discrepancies, but evidence is lacking for nonmodel organisms. Here, we explored the intersection of genetics and gene regulation in admixed genomes derived from an experimental cross between a western gray wolf and western coyote. We found a significant positive association between methylation and wolf ancestry, and identified outlier genes that have been previously implicated in inbreeding-related, or otherwise deleterious, phenotypes. We describe a pattern of site-specific, rather than genome-wide, methylation driven by inter-specific hybridization. Epigenetic variation is thus suggested to play a nontrivial role in both maintaining and combating mismatched genotypes through putative transcriptional mechanisms. We conclude that the regulation of gene expression is an underappreciated key component of hybrid genome functioning, but could also act as a potential source of novel and beneficial adaptive variation in hybrid offspring. © The American Genetic Association 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic Diversity and Phenotypic Variation for Drought Resistance in Alfalfa (Medicago sativa L.) Germplasm Collected for Drought Tolerance

USDA-ARS?s Scientific Manuscript database

Drought is a major environmental factor hampering alfalfa productivity worldwide. Gene banks provide an array of trait diversity, frequently consisting of specific seed collection projects that focused on acquiring germplasm adapted to specific traits such as drought tolerance. These subsets provide...

Geographic patterns of genetic variation and conservation consequences in three South American rodents.

PubMed

Miranda, Gustavo B; Andrades-Miranda, Jaqueline; Oliveira, Luiz F B; Langguth, Alfredo; Mattevi, Margarete S

2007-12-01

In this study, the geographic patterns of genetic variation of three rodent species belonging to the tribe Oryzomyini were investigated using the mitochondrial cytochrome b and nuclear IRBP genes in biomes that are undergoing degradation processes to a greater or lesser degree. The samples are from 25 collecting localities distributed throughout the Amazon, Cerrado, Atlantic Forest, and Pampa biomes. The results show that the three species have a population and geographic structure, besides being in demographic equilibrium. The phylogenetic analyses performed on Euryoryzomys russatus and Hylaeamys megacephalus showed these specimens grouped in three distinct clades forming geographic gradients (North-South direction in H. megacephalus). Intraspecific genetic divergence was higher in H. megacephalus (4.53%), followed by E. russatus (1.79%), and lowest in Sooretamys angouya (0.88%). The results obtained indicate that, necessarily, the management strategies to preserve genetic diversity should be different for each species, since each of them presented specific population parameters.

Deep Brain Stimulation for Dystonia: A Novel Perspective on the Value of Genetic Testing

PubMed Central

Jinnah, H. A.; Alterman, Ron; Klein, Christine; Krauss, Joachim K.; Moro, Elena; Vidailhet, Marie; Raike, Robert

2017-01-01

The dystonias are a group of disorders characterized by excessive muscle contractions leading to abnormal movements and postures. There are many different clinical manifestations and underlying causes. Deep brain stimulation (DBS) provides an effect treatment, but outcomes can vary considerably among the different subtypes of dystonia. Several variables are thought to contribute to this variation including age of onset and duration of dystonia, specific characteristics of the dystonic movements, location of stimulation and stimulator settings, and others. The potential contributions of genetic factors have received little attention. In this review, we summarize evidence that some of the variation in DBS outcomes for dystonia is due to genetic factors. The evidence suggests that more methodical genetic testing may provide useful information in the assessment of potential surgical candidates, and in advancing our understanding of the biological mechanisms that influence DBS outcomes. PMID:28160152

Mind the gut: genomic insights to population divergence and gut microbial composition of two marine keystone species.

PubMed

Fietz, Katharina; Rye Hintze, Christian Olaf; Skovrind, Mikkel; Kjærgaard Nielsen, Tue; Limborg, Morten T; Krag, Marcus A; Palsbøll, Per J; Hestbjerg Hansen, Lars; Rask Møller, Peter; Gilbert, M Thomas P

2018-05-02

Deciphering the mechanisms governing population genetic divergence and local adaptation across heterogeneous environments is a central theme in marine ecology and conservation. While population divergence and ecological adaptive potential are classically viewed at the genetic level, it has recently been argued that their microbiomes may also contribute to population genetic divergence. We explored whether this might be plausible along the well-described environmental gradient of the Baltic Sea in two species of sand lance (Ammodytes tobianus and Hyperoplus lanceolatus). Specifically, we assessed both their population genetic and gut microbial composition variation and investigated not only which environmental parameters correlate with the observed variation, but whether host genome also correlates with microbiome variation. We found a clear genetic structure separating the high-salinity North Sea from the low-salinity Baltic Sea sand lances. The observed genetic divergence was not simply a function of isolation by distance, but correlated with environmental parameters, such as salinity, sea surface temperature, and, in the case of A. tobianus, possibly water microbiota. Furthermore, we detected two distinct genetic groups in Baltic A. tobianus that might represent sympatric spawning types. Investigation of possible drivers of gut microbiome composition variation revealed that host species identity was significantly correlated with the microbial community composition of the gut. A potential influence of host genetic factors on gut microbiome composition was further confirmed by the results of a constrained analysis of principal coordinates. The host genetic component was among the parameters that best explain observed variation in gut microbiome composition. Our findings have relevance for the population structure of two commercial species but also provide insights into potentially relevant genomic and microbial factors with regards to sand lance adaptation across the North Sea-Baltic Sea environmental gradient. Furthermore, our findings support the hypothesis that host genetics may play a role in regulating the gut microbiome at both the interspecific and intraspecific levels. As sequencing costs continue to drop, we anticipate that future studies that include full genome and microbiome sequencing will be able to explore the full relationship and its potential adaptive implications for these species.

Genetic variation facilitates seedling establishment but not population growth rate of a perennial invader

PubMed Central

Li, Shou-Li; Vasemägi, Anti; Ramula, Satu

2016-01-01

Background and Aims Assessing the demographic consequences of genetic variation is fundamental to invasion biology. However, genetic and demographic approaches are rarely combined to explore the effects of genetic variation on invasive populations in natural environments. This study combined population genetics, demographic data and a greenhouse experiment to investigate the consequences of genetic variation for the population fitness of the perennial, invasive herb Lupinus polyphyllus. Methods Genetic and demographic data were collected from 37 L. polyphyllus populations representing different latitudes in Finland, and genetic variation was characterized based on 13 microsatellite loci. Associations between genetic variation and population size, population density, latitude and habitat were investigated. Genetic variation was then explored in relation to four fitness components (establishment, survival, growth, fecundity) measured at the population level, and the long-term population growth rate (λ). For a subset of populations genetic variation was also examined in relation to the temporal variability of λ. A further assessment was made of the role of natural selection in the observed variation of certain fitness components among populations under greenhouse conditions. Key Results It was found that genetic variation correlated positively with population size, particularly at higher latitudes, and differed among habitat types. Average seedling establishment per population increased with genetic variation in the field, but not under greenhouse conditions. Quantitative genetic divergence (QST) based on seedling establishment in the greenhouse was smaller than allelic genetic divergence (F′ST), indicating that unifying selection has a prominent role in this fitness component. Genetic variation was not associated with average survival, growth or fecundity measured at the population level, λ or its variability. Conclusions The study suggests that although genetic variation may facilitate plant invasions by increasing seedling establishment, it may not necessarily affect the long-term population growth rate. Therefore, established invasions may be able to grow equally well regardless of their genetic diversity. PMID:26420202

Clan, Language, and Migration History Has Shaped Genetic Diversity in Haida and Tlingit Populations From Southeast Alaska

PubMed Central

Schurr, Theodore G.; Dulik, Matthew C.; Owings, Amanda C.; Zhadanov, Sergey I.; Gaieski, Jill B.; Vilar, Miguel G.; Ramos, Judy; Moss, Mary Beth; Natkong, Francis

2013-01-01

The linguistically distinctive Haida and Tlingit tribes of Southeast Alaska are known for their rich material culture, complex social organization, and elaborate ritual practices. However, much less is known about these tribes from a population genetic perspective. For this reason, we analyzed mtDNA and Y-chromosome variation in Haida and Tlingit populations to elucidate several key issues pertaining to the history of this region. These included the genetic relationships of Haida and Tlingit to other indigenous groups in Alaska and Canada; the relationship between linguistic and genetic data for populations assigned to the Na-Dene linguistic family, specifically, the inclusion of Haida with Athapaskan, Eyak, and Tlingit in the language family; the possible influence of matrilineal clan structure on patterns of genetic variation in Haida and Tlingit populations; and the impact of European entry into the region on the genetic diversity of these indigenous communities. Our analysis indicates that, while sharing a “northern” genetic profile, the Haida and the Tlingit are genetically distinctive from each other. In addition, Tlingit groups themselves differ across their geographic range, in part due to interactions of Tlingit tribes with Athapaskan and Eyak groups to the north. The data also reveal a strong influence of maternal clan identity on mtDNA variation in these groups, as well as the significant influence of non-native males on Y-chromosome diversity. These results yield new details about the histories of the Haida and Tlingit tribes in this region. PMID:22549307

Genomic atlas of the human plasma proteome.

PubMed

Sun, Benjamin B; Maranville, Joseph C; Peters, James E; Stacey, David; Staley, James R; Blackshaw, James; Burgess, Stephen; Jiang, Tao; Paige, Ellie; Surendran, Praveen; Oliver-Williams, Clare; Kamat, Mihir A; Prins, Bram P; Wilcox, Sheri K; Zimmerman, Erik S; Chi, An; Bansal, Narinder; Spain, Sarah L; Wood, Angela M; Morrell, Nicholas W; Bradley, John R; Janjic, Nebojsa; Roberts, David J; Ouwehand, Willem H; Todd, John A; Soranzo, Nicole; Suhre, Karsten; Paul, Dirk S; Fox, Caroline S; Plenge, Robert M; Danesh, John; Runz, Heiko; Butterworth, Adam S

2018-06-01

Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as well as with disease-associated loci, and find evidence that protein biomarkers have causal roles in disease using Mendelian randomization analysis. By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development.

Nature, Nurture and Evolution of Intra-Species Variation in Mosquito Arbovirus Transmission Competence

PubMed Central

Tabachnick, Walter J.

2013-01-01

Mosquitoes vary in their competence or ability to transmit arthropod-borne viruses (arboviruses). Many arboviruses cause disease in humans and animals. Identifying the environmental and genetic causes of variation in mosquito competence for arboviruses is one of the great challenges in public health. Progress identifying genetic (nature) and environmental (nurture) factors influencing mosquito competence for arboviruses is reviewed. There is great complexity in the various traits that comprise mosquito competence. The complex interactions between environmental and genetic factors controlling these traits and the factors shaping variation in Nature are largely unknown. The norms of reaction of specific genes influencing competence, their distributions in natural populations and the effects of genetic polymorphism on phenotypic variation need to be determined. Mechanisms influencing competence are not likely due to natural selection because of the direct effects of the arbovirus on mosquito fitness. More likely the traits for mosquito competence for arboviruses are the effects of adaptations for other functions of these competence mechanisms. Determining these other functions is essential to understand the evolution and distributions of competence for arboviruses. This information is needed to assess risk from mosquito-borne disease, predict new mosquito-arbovirus systems, and provide novel strategies to mitigate mosquito-borne arbovirus transmission. PMID:23343982

Genetic Mapping of Quantitative Trait Loci Controlling Growth and Wood Quality Traits in Eucalyptus Grandis Using a Maternal Half-Sib Family and Rapd Markers

PubMed Central

Grattapaglia, D.; Bertolucci, FLG.; Penchel, R.; Sederoff, R. R.

1996-01-01

Quantitative trait loci (QTL) mapping of forest productivity traits was performed using an open pollinated half-sib family of Eucalyptus grandis. For volume growth, a sequential QTL mapping approach was applied using bulk segregant analysis (BSA), selective genotyping (SG) and cosegregation analysis (CSA). Despite the low heritability of this trait and the heterogeneous genetic background employed for mapping. BSA detected one putative QTL and SG two out of the three later found by CSA. The three putative QTL for volume growth were found to control 13.7% of the phenotypic variation, corresponding to an estimated 43.7% of the genetic variation. For wood specific gravity five QTL were identified controlling 24.7% of the phenotypic variation corresponding to 49% of the genetic variation. Overlapping QTL for CBH, WSG and percentage dry weight of bark were observed. A significant case of digenic epistasis was found, involving unlinked QTL for volume. Our results demonstrate the applicability of the within half-sib design for QTL mapping in forest trees and indicate the existence of major genes involved in the expression of economically important traits related to forest productivity in Eucalyptus grandis. These findings have important implications for marker-assisted tree breeding. PMID:8913761

Quantitative Resistance: More Than Just Perception of a Pathogen

PubMed Central

2017-01-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. PMID:28302676

AGAPE (Automated Genome Analysis PipelinE) for Pan-Genome Analysis of Saccharomyces cerevisiae

PubMed Central

Song, Giltae; Dickins, Benjamin J. A.; Demeter, Janos; Engel, Stacia; Dunn, Barbara; Cherry, J. Michael

2015-01-01

The characterization and public release of genome sequences from thousands of organisms is expanding the scope for genetic variation studies. However, understanding the phenotypic consequences of genetic variation remains a challenge in eukaryotes due to the complexity of the genotype-phenotype map. One approach to this is the intensive study of model systems for which diverse sources of information can be accumulated and integrated. Saccharomyces cerevisiae is an extensively studied model organism, with well-known protein functions and thoroughly curated phenotype data. To develop and expand the available resources linking genomic variation with function in yeast, we aim to model the pan-genome of S. cerevisiae. To initiate the yeast pan-genome, we newly sequenced or re-sequenced the genomes of 25 strains that are commonly used in the yeast research community using advanced sequencing technology at high quality. We also developed a pipeline for automated pan-genome analysis, which integrates the steps of assembly, annotation, and variation calling. To assign strain-specific functional annotations, we identified genes that were not present in the reference genome. We classified these according to their presence or absence across strains and characterized each group of genes with known functional and phenotypic features. The functional roles of novel genes not found in the reference genome and associated with strains or groups of strains appear to be consistent with anticipated adaptations in specific lineages. As more S. cerevisiae strain genomes are released, our analysis can be used to collate genome data and relate it to lineage-specific patterns of genome evolution. Our new tool set will enhance our understanding of genomic and functional evolution in S. cerevisiae, and will be available to the yeast genetics and molecular biology community. PMID:25781462

Exploiting genomics and natural genetic variation to decode macrophage enhancers

PubMed Central

Romanoski, Casey E.; Link, Verena M.; Heinz, Sven; Glass, Christopher K.

2015-01-01

The mammalian genome contains on the order of a million enhancer-like regions that are required to establish the identities and functions of specific cell types. Here, we review recent studies in immune cells that have provided insight into the mechanisms that selectively activate certain enhancers in response to cell lineage and environmental signals. We describe a working model wherein distinct classes of transcription factors define the repertoire of active enhancers in macrophages through collaborative and hierarchical interactions, and discuss important challenges to this model, specifically providing examples from T cells. We conclude by discussing the use of natural genetic variation as a powerful approach for decoding transcription factor combinations that play dominant roles in establishing the enhancer landscapes, and the potential that these insights have for advancing our understanding of the molecular causes of human disease. PMID:26298065

QTL mapping for sexually dimorphic fitness-related traits in wild bighorn sheep

PubMed Central

Poissant, J; Davis, C S; Malenfant, R M; Hogg, J T; Coltman, D W

2012-01-01

Dissecting the genetic architecture of fitness-related traits in wild populations is key to understanding evolution and the mechanisms maintaining adaptive genetic variation. We took advantage of a recently developed genetic linkage map and phenotypic information from wild pedigreed individuals from Ram Mountain, Alberta, Canada, to study the genetic architecture of ecologically important traits (horn volume, length, base circumference and body mass) in bighorn sheep. In addition to estimating sex-specific and cross-sex quantitative genetic parameters, we tested for the presence of quantitative trait loci (QTLs), colocalization of QTLs between bighorn sheep and domestic sheep, and sex × QTL interactions. All traits showed significant additive genetic variance and genetic correlations tended to be positive. Linkage analysis based on 241 microsatellite loci typed in 310 pedigreed animals resulted in no significant and five suggestive QTLs (four for horn dimension on chromosomes 1, 18 and 23, and one for body mass on chromosome 26) using genome-wide significance thresholds (Logarithm of odds (LOD) >3.31 and >1.88, respectively). We also confirmed the presence of a horn dimension QTL in bighorn sheep at the only position known to contain a similar QTL in domestic sheep (on chromosome 10 near the horns locus; nominal P<0.01) and highlighted a number of regions potentially containing weight-related QTLs in both species. As expected for sexually dimorphic traits involved in male–male combat, loci with sex-specific effects were detected. This study lays the foundation for future work on adaptive genetic variation and the evolutionary dynamics of sexually dimorphic traits in bighorn sheep. PMID:21847139

Genetic Architecture of the Variation in Male-Specific Ossified Processes on the Anal Fins of Japanese Medaka.

PubMed

Kawajiri, Maiko; Fujimoto, Shingo; Yoshida, Kohta; Yamahira, Kazunori; Kitano, Jun

2015-10-28

Traits involved in reproduction evolve rapidly and show great diversity among closely related species. However, the genetic mechanisms that underlie the diversification of courtship traits are mostly unknown. Japanese medaka fishes (Oryzias latipes) use anal fins to attract females and to grasp females during courtship; the males have longer anal fins with male-specific ossified papillary processes on the fin rays. However, anal fin morphology varies between populations: the southern populations tend to have longer anal fins and more processes than the northern populations. In the present study, we conducted quantitative trait locus (QTL) mapping to investigate the genetic architecture underlying the variation in the number of papillary processes of Japanese medaka fish and compared the QTL with previously identified QTL controlling anal fin length. First, we found that only a few QTL were shared between anal fin length and papillary process number. Second, we found that the numbers of papillary processes on different fin rays often were controlled by different QTL. Finally, we produced another independent cross and found that some QTL were repeatable between the two crosses, whereas others were specific to only one cross. These results suggest that variation in the number of papillary processes is polygenic and controlled by QTL that are distinct from those controlling anal fin length. Thus, different courtship traits in Japanese medaka share a small number of QTL and have the potential for independent evolution. Copyright © 2015 Kawajiri et al.

Levels of genetic diversity and taxonomic status of Epinephelus species in United Arab Emirates fish markets.

PubMed

Ketchum, Remi N; Dieng, Mame M; Vaughan, Grace O; Burt, John A; Idaghdour, Youssef

2016-04-30

Understanding the patterns of genetic diversity of fish species is essential for marine conservation and management. This is particularly important in the Arabian Gulf where marine life is subject to extreme environmental conditions that could impact genetic diversity. Here we assess genetic diversity of the most commercially important fish in the United Arab Emirates; groupers (Epinephelus spp.). Sequencing of 973 bp mitochondrial DNA from 140 tissue samples collected in four main fish markets revealed 58 haplotypes clustered within three groups. Data analysis revealed the presence of three distinct Epinephelus species being marketed as one species (hammour): Epinephelus coioides, Epinephelus areolatus and Epinephelus bleekeri. We report species-specific genetic markers and demonstrate that all three species exhibit relatively low levels of genetic variation, reflecting the effect of overfishing and environmental pressures. In light of the genetic evidence presented here, conservation and management of groupers in the UAE warrant the implementation of species-specific measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantifying Temporal Genomic Erosion in Endangered Species.

PubMed

Díez-Del-Molino, David; Sánchez-Barreiro, Fatima; Barnes, Ian; Gilbert, M Thomas P; Dalén, Love

2018-03-01

Many species have undergone dramatic population size declines over the past centuries. Although stochastic genetic processes during and after such declines are thought to elevate the risk of extinction, comparative analyses of genomic data from several endangered species suggest little concordance between genome-wide diversity and current population sizes. This is likely because species-specific life-history traits and ancient bottlenecks overshadow the genetic effect of recent demographic declines. Therefore, we advocate that temporal sampling of genomic data provides a more accurate approach to quantify genetic threats in endangered species. Specifically, genomic data from predecline museum specimens will provide valuable baseline data that enable accurate estimation of recent decreases in genome-wide diversity, increases in inbreeding levels, and accumulation of deleterious genetic variation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Eco-geographical diversification of bitter taste receptor genes (TAS2Rs) among subspecies of chimpanzees (Pan troglodytes).

PubMed

Hayakawa, Takashi; Sugawara, Tohru; Go, Yasuhiro; Udono, Toshifumi; Hirai, Hirohisa; Imai, Hiroo

2012-01-01

Chimpanzees (Pan troglodytes) have region-specific difference in dietary repertoires from East to West across tropical Africa. Such differences may result from different genetic backgrounds in addition to cultural variations. We analyzed the sequences of all bitter taste receptor genes (cTAS2Rs) in a total of 59 chimpanzees, including 4 putative subspecies. We identified genetic variations including single-nucleotide variations (SNVs), insertions and deletions (indels), gene-conversion variations, and copy-number variations (CNVs) in cTAS2Rs. Approximately two-thirds of all cTAS2R haplotypes in the amino acid sequence were unique to each subspecies. We analyzed the evolutionary backgrounds of natural selection behind such diversification. Our previous study concluded that diversification of cTAS2Rs in western chimpanzees (P. t. verus) may have resulted from balancing selection. In contrast, the present study found that purifying selection dominates as the evolutionary form of diversification of the so-called human cluster of cTAS2Rs in eastern chimpanzees (P. t. schweinfurthii) and that the other cTAS2Rs were under no obvious selection as a whole. Such marked diversification of cTAS2Rs with different evolutionary backgrounds among subspecies of chimpanzees probably reflects their subspecies-specific dietary repertoires.

Eco-Geographical Diversification of Bitter Taste Receptor Genes (TAS2Rs) among Subspecies of Chimpanzees (Pan troglodytes)

PubMed Central

Hayakawa, Takashi; Sugawara, Tohru; Go, Yasuhiro; Udono, Toshifumi; Hirai, Hirohisa; Imai, Hiroo

2012-01-01

Chimpanzees (Pan troglodytes) have region-specific difference in dietary repertoires from East to West across tropical Africa. Such differences may result from different genetic backgrounds in addition to cultural variations. We analyzed the sequences of all bitter taste receptor genes (cTAS2Rs) in a total of 59 chimpanzees, including 4 putative subspecies. We identified genetic variations including single-nucleotide variations (SNVs), insertions and deletions (indels), gene-conversion variations, and copy-number variations (CNVs) in cTAS2Rs. Approximately two-thirds of all cTAS2R haplotypes in the amino acid sequence were unique to each subspecies. We analyzed the evolutionary backgrounds of natural selection behind such diversification. Our previous study concluded that diversification of cTAS2Rs in western chimpanzees (P. t. verus) may have resulted from balancing selection. In contrast, the present study found that purifying selection dominates as the evolutionary form of diversification of the so-called human cluster of cTAS2Rs in eastern chimpanzees (P. t. schweinfurthii) and that the other cTAS2Rs were under no obvious selection as a whole. Such marked diversification of cTAS2Rs with different evolutionary backgrounds among subspecies of chimpanzees probably reflects their subspecies-specific dietary repertoires. PMID:22916235

Personalized biochemistry and biophysics.

PubMed

Kroncke, Brett M; Vanoye, Carlos G; Meiler, Jens; George, Alfred L; Sanders, Charles R

2015-04-28

Whole human genome sequencing of individuals is becoming rapid and inexpensive, enabling new strategies for using personal genome information to help diagnose, treat, and even prevent human disorders for which genetic variations are causative or are known to be risk factors. Many of the exploding number of newly discovered genetic variations alter the structure, function, dynamics, stability, and/or interactions of specific proteins and RNA molecules. Accordingly, there are a host of opportunities for biochemists and biophysicists to participate in (1) developing tools to allow accurate and sometimes medically actionable assessment of the potential pathogenicity of individual variations and (2) establishing the mechanistic linkage between pathogenic variations and their physiological consequences, providing a rational basis for treatment or preventive care. In this review, we provide an overview of these opportunities and their associated challenges in light of the current status of genomic science and personalized medicine, the latter often termed precision medicine.

Personalized Biochemistry and Biophysics

PubMed Central

2016-01-01

Whole human genome sequencing of individuals is becoming rapid and inexpensive, enabling new strategies for using personal genome information to help diagnose, treat, and even prevent human disorders for which genetic variations are causative or are known to be risk factors. Many of the exploding number of newly discovered genetic variations alter the structure, function, dynamics, stability, and/or interactions of specific proteins and RNA molecules. Accordingly, there are a host of opportunities for biochemists and biophysicists to participate in (1) developing tools to allow accurate and sometimes medically actionable assessment of the potential pathogenicity of individual variations and (2) establishing the mechanistic linkage between pathogenic variations and their physiological consequences, providing a rational basis for treatment or preventive care. In this review, we provide an overview of these opportunities and their associated challenges in light of the current status of genomic science and personalized medicine, the latter often termed precision medicine. PMID:25856502

The Brassica oleracea genome reveals the asymmetrical evolution of polyploid genomes

PubMed Central

Liu, Shengyi; Liu, Yumei; Yang, Xinhua; Tong, Chaobo; Edwards, David; Parkin, Isobel A. P.; Zhao, Meixia; Ma, Jianxin; Yu, Jingyin; Huang, Shunmou; Wang, Xiyin; Wang, Junyi; Lu, Kun; Fang, Zhiyuan; Bancroft, Ian; Yang, Tae-Jin; Hu, Qiong; Wang, Xinfa; Yue, Zhen; Li, Haojie; Yang, Linfeng; Wu, Jian; Zhou, Qing; Wang, Wanxin; King, Graham J; Pires, J. Chris; Lu, Changxin; Wu, Zhangyan; Sampath, Perumal; Wang, Zhuo; Guo, Hui; Pan, Shengkai; Yang, Limei; Min, Jiumeng; Zhang, Dong; Jin, Dianchuan; Li, Wanshun; Belcram, Harry; Tu, Jinxing; Guan, Mei; Qi, Cunkou; Du, Dezhi; Li, Jiana; Jiang, Liangcai; Batley, Jacqueline; Sharpe, Andrew G; Park, Beom-Seok; Ruperao, Pradeep; Cheng, Feng; Waminal, Nomar Espinosa; Huang, Yin; Dong, Caihua; Wang, Li; Li, Jingping; Hu, Zhiyong; Zhuang, Mu; Huang, Yi; Huang, Junyan; Shi, Jiaqin; Mei, Desheng; Liu, Jing; Lee, Tae-Ho; Wang, Jinpeng; Jin, Huizhe; Li, Zaiyun; Li, Xun; Zhang, Jiefu; Xiao, Lu; Zhou, Yongming; Liu, Zhongsong; Liu, Xuequn; Qin, Rui; Tang, Xu; Liu, Wenbin; Wang, Yupeng; Zhang, Yangyong; Lee, Jonghoon; Kim, Hyun Hee; Denoeud, France; Xu, Xun; Liang, Xinming; Hua, Wei; Wang, Xiaowu; Wang, Jun; Chalhoub, Boulos; Paterson, Andrew H

2014-01-01

Polyploidization has provided much genetic variation for plant adaptive evolution, but the mechanisms by which the molecular evolution of polyploid genomes establishes genetic architecture underlying species differentiation are unclear. Brassica is an ideal model to increase knowledge of polyploid evolution. Here we describe a draft genome sequence of Brassica oleracea, comparing it with that of its sister species B. rapa to reveal numerous chromosome rearrangements and asymmetrical gene loss in duplicated genomic blocks, asymmetrical amplification of transposable elements, differential gene co-retention for specific pathways and variation in gene expression, including alternative splicing, among a large number of paralogous and orthologous genes. Genes related to the production of anticancer phytochemicals and morphological variations illustrate consequences of genome duplication and gene divergence, imparting biochemical and morphological variation to B. oleracea. This study provides insights into Brassica genome evolution and will underpin research into the many important crops in this genus. PMID:24852848

Genomic determinants of epidermal appendage patterning and structure in domestic birds

PubMed Central

Boer, Elena F.; Van Hollebeke, Hannah F.; Shapiro, Michael D.

2017-01-01

Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity. PMID:28347644

Cryptic Genetic Variation for Arabidopsis thaliana Seed Germination Speed in a Novel Salt Stress Environment

PubMed Central

Yuan, Wei; Flowers, Jonathan M.; Sahraie, Dustin J.; Purugganan, Michael D.

2016-01-01

The expansion of species ranges frequently necessitates responses to novel environments. In plants, the ability of seeds to disperse to marginal areas relies in part to its ability to germinate under stressful conditions. Here we examine the genetic architecture of Arabidopsis thaliana germination speed under a novel, saline environment, using an Extreme QTL (X-QTL) mapping platform we previously developed. We find that early germination in normal and salt conditions both rely on a QTL on the distal arm of chromosome 4, but we also find unique QTL on chromosomes 1, 2, 4, and 5 that are specific to salt stress environments. Moreover, different QTLs are responsible for early vs. late germination, suggesting a temporal component to the expression of life history under these stress conditions. Our results indicate that cryptic genetic variation exists for responses to a novel abiotic stress, which may suggest a role of such variation in adaptation to new climactic conditions or growth environments. PMID:27543295

Sex Differences in Magical Ideation: A Community-Based Twin Study

PubMed Central

Karcher, Nicole R.; Slutske, Wendy S.; Kerns, John G.; Piasecki, Thomas M.; Martin, Nicholas G.

2014-01-01

Two questions regarding sex differences in magical ideation were investigated in this study: (1) whether there are mean level sex differences on the Magical Ideation Scale (MIS), and (2) whether there are quantitative and/or qualitative sex differences in the genetic contributions to variation on this scale. These questions were evaluated using data obtained from a large community sample of adult Australian twins (N=4,355) that included opposite-sex pairs. Participants completed a modified 15-item version of the MIS within a larger assessment battery. Women reported both higher means and variability on the MIS than men; this was also observed within families (in opposite-sex twin pairs). Biometric modeling indicated that the proportion of variation in MIS scores due to genetic influences (indicating quantitative sex differences) and the specific latent genetic contributions to this variation (indicating qualitative sex differences) were the same in men and women. These findings clarify the nature of sex differences in magical ideation and point to avenues for future research. PMID:24364500

Mountain pine beetle voltinism and life history characteristics across latitudinal and elevational gradients in the western United States

Treesearch

Barbara Bentz; James Vandygriff; Camille Jensen; Tom Coleman; Patricia Maloney; Sheri Smith; Amanda Grady; Greta Schen-Langenheim

2014-01-01

Substantial genetic variation in development time is known to exist among mountain pine beetle (Dendroctonus ponderosae Hopkins) populations across the western United States. The effect of this variation on geographic patterns in voltinism (generation time) and thermal requirements to produce specific voltinism pathways have not been investigated. The influence of...

Chemical and mechanical defenses vary among maternal lines and leaf ages in Verbascum thapsus L. (Scrophulariaceae) and reduce palatability to a generalist insect

USDA-ARS?s Scientific Manuscript database

Intra-specific variation in host-plant quality affects herbivore foraging decisions and, because of this, can feed back to shape plant fitness. In particular, among- and within plant variation in defense shapes herbivore behavior, and if genetically based, may respond to natural selection by herbivo...

Upper Secondary Students' Understanding of the Use of Multiple Models in Biology Textbooks--The Importance of Conceptual Variation and Incommensurability

ERIC Educational Resources Information Center

Gericke, Niklas; Hagberg, Mariana; Jorde, Doris

2013-01-01

In this study we investigate students' ability to discern conceptual variation and the use of multiple models in genetics when reading content-specific excerpts from biology textbooks. Using the history and philosophy of science as our reference, we were able to develop a research instrument allowing students themselves to investigate the…

Bayesian Inference of Allele-Specific Gene Expression Indicates Abundant Cis-Regulatory Variation in Natural Flycatcher Populations

PubMed Central

Wang, Mi

2017-01-01

Abstract Polymorphism in cis-regulatory sequences can lead to different levels of expression for the two alleles of a gene, providing a starting point for the evolution of gene expression. Little is known about the genome-wide abundance of genetic variation in gene regulation in natural populations but analysis of allele-specific expression (ASE) provides a means for investigating such variation. We performed RNA-seq of multiple tissues from population samples of two closely related flycatcher species and developed a Bayesian algorithm that maximizes data usage by borrowing information from the whole data set and combines several SNPs per transcript to detect ASE. Of 2,576 transcripts analyzed in collared flycatcher, ASE was detected in 185 (7.2%) and a similar frequency was seen in the pied flycatcher. Transcripts with statistically significant ASE commonly showed the major allele in >90% of the reads, reflecting that power was highest when expression was heavily biased toward one of the alleles. This would suggest that the observed frequencies of ASE likely are underestimates. The proportion of ASE transcripts varied among tissues, being lowest in testis and highest in muscle. Individuals often showed ASE of particular transcripts in more than one tissue (73.4%), consistent with a genetic basis for regulation of gene expression. The results suggest that genetic variation in regulatory sequences commonly affects gene expression in natural populations and that it provides a seedbed for phenotypic evolution via divergence in gene expression. PMID:28453623

Evidence that Magnetic Navigation and Geomagnetic Imprinting Shape Spatial Genetic Variation in Sea Turtles.

PubMed

Brothers, J Roger; Lohmann, Kenneth J

2018-04-23

The canonical drivers of population genetic structure, or spatial genetic variation, are isolation by distance and isolation by environment. Isolation by distance predicts that neighboring populations will be genetically similar and geographically distant populations will be genetically distinct [1]. Numerous examples also exist of isolation by environment, a phenomenon in which populations that inhabit similar environments (e.g., same elevation, temperature, or vegetation) are genetically similar even if they are distant, whereas populations that inhabit different environments are genetically distinct even when geographically close [2-4]. These dual models provide a widely accepted conceptual framework for understanding population structure [5-8]. Here, we present evidence for an additional, novel process that we call isolation by navigation, in which the navigational mechanism used by a long-distance migrant influences population structure independently of isolation by either distance or environment. Specifically, we investigated the population structure of loggerhead sea turtles (Caretta caretta) [9], which return to nest on their natal beaches by seeking out unique magnetic signatures along the coast-a behavior known as geomagnetic imprinting [10-12]. Results reveal that spatial variation in Earth's magnetic field strongly predicts genetic differentiation between nesting beaches, even when environmental similarities and geographic proximity are taken into account. The findings provide genetic corroboration of geomagnetic imprinting [10, 13]. Moreover, they provide strong evidence that geomagnetic imprinting and magnetic navigation help shape the population structure of sea turtles and perhaps numerous other long-distance migrants that return to their natal areas to reproduce [13-17]. Copyright © 2018 Elsevier Ltd. All rights reserved.

Red Wine Consumption is inversely associated with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA Adduct Levels in Prostate

PubMed Central

Rybicki, Benjamin A.; Neslund-Dudas, Christine; Bock, Cathryn H.; Nock, Nora L.; Rundle, Andrew; Jankowski, Michelle; Levin, Albert M.; Beebe-Dimmer, Jennifer; Savera, Adnan T.; Takahashi, Satoru; Shirai, Tomoyuki; Tang, Deliang

2011-01-01

In humans, genetic variation and dietary factors may alter the biologic effects of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the major heterocyclic amines generated from cooking meats at high temperatures that has carcinogenic potential through the formation of DNA adducts. Previously, we reported grilled red meat consumption associated with PhIP-DNA adduct levels in human prostate. In the present study, we expanded our investigation to estimate the associations between beverage consumption and PhIP-DNA adduct levels in prostate for 391 prostate cancer cases. Of the 15 beverages analyzed, red wine consumption had the strongest association with PhIP-DNA adduct levels showing an inverse correlation in both tumor (p=0.006) and non-tumor (p=0.002) prostate cells. Red wine consumption differed significantly between African-American and white cases, but PhIP-DNA adduct levels in prostate did not vary by race. In African Americans compared with whites, however, associations between red wine consumption and PhIP-DNA adduct levels were not as strong as associations with specific (e.g., SULT1A1 and UGT1A10 genotypes) and non-specific (e.g., African ancestry) genetic variation. In a multivariable model, the covariate for red wine consumption explained a comparable percentage (13-16%) of the variation in PhIP-DNA adduct levels in prostate across the two racial groups, but the aforementioned genetic factors explained 33% of the PhIP-DNA adduct variation in African-American cases, while only 19% of the PhIPDNA adduct variation in whites. We conclude that red wine consumption may counteract biologic effects of PhIP exposure in human prostate, but genetic factors may play an even larger role, particularly in African Americans. PMID:21846795

Contribution of trans regulatory eQTL to cryptic genetic variation in C. elegans.

PubMed

Snoek, Basten L; Sterken, Mark G; Bevers, Roel P J; Volkers, Rita J M; Van't Hof, Arjen; Brenchley, Rachel; Riksen, Joost A G; Cossins, Andrew; Kammenga, Jan E

2017-06-29

Cryptic genetic variation (CGV) is the hidden genetic variation that can be unlocked by perturbing normal conditions. CGV can drive the emergence of novel complex phenotypes through changes in gene expression. Although our theoretical understanding of CGV has thoroughly increased over the past decade, insight into polymorphic gene expression regulation underlying CGV is scarce. Here we investigated the transcriptional architecture of CGV in response to rapid temperature changes in the nematode Caenorhabditis elegans. We analyzed regulatory variation in gene expression (and mapped eQTL) across the course of a heat stress and recovery response in a recombinant inbred population. We measured gene expression over three temperature treatments: i) control, ii) heat stress, and iii) recovery from heat stress. Compared to control, exposure to heat stress affected the transcription of 3305 genes, whereas 942 were affected in recovering animals. These affected genes were mainly involved in metabolism and reproduction. The gene expression pattern in recovering animals resembled both the control and the heat-stress treatment. We mapped eQTL using the genetic variation of the recombinant inbred population and detected 2626 genes with an eQTL in the heat-stress treatment, 1797 in the control, and 1880 in the recovery. The cis-eQTL were highly shared across treatments. A considerable fraction of the trans-eQTL (40-57%) mapped to 19 treatment specific trans-bands. In contrast to cis-eQTL, trans-eQTL were highly environment specific and thus cryptic. Approximately 67% of the trans-eQTL were only induced in a single treatment, with heat-stress showing the most unique trans-eQTL. These results illustrate the highly dynamic pattern of CGV across three different environmental conditions that can be evoked by a stress response over a relatively short time-span (2 h) and that CGV is mainly determined by response related trans regulatory eQTL.

Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis

PubMed Central

Ghazanfar, Shila; Vuocolo, Tony; Morrison, Janna L.; Nicholas, Lisa M.; McMillen, Isabella C.; Yang, Jean Y. H.; Buckley, Michael J.

2017-01-01

Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population. PMID:28665992

Modeling Host Genetic Regulation of Influenza Pathogenesis in the Collaborative Cross

PubMed Central

Ferris, Martin T.; Aylor, David L.; Bottomly, Daniel; Whitmore, Alan C.; Aicher, Lauri D.; Bell, Timothy A.; Bradel-Tretheway, Birgit; Bryan, Janine T.; Buus, Ryan J.; Gralinski, Lisa E.; Haagmans, Bart L.; McMillan, Leonard; Miller, Darla R.; Rosenzweig, Elizabeth; Valdar, William; Wang, Jeremy; Churchill, Gary A.; Threadgill, David W.; McWeeney, Shannon K.; Katze, Michael G.; Pardo-Manuel de Villena, Fernando; Baric, Ralph S.; Heise, Mark T.

2013-01-01

Genetic variation contributes to host responses and outcomes following infection by influenza A virus or other viral infections. Yet narrow windows of disease symptoms and confounding environmental factors have made it difficult to identify polymorphic genes that contribute to differential disease outcomes in human populations. Therefore, to control for these confounding environmental variables in a system that models the levels of genetic diversity found in outbred populations such as humans, we used incipient lines of the highly genetically diverse Collaborative Cross (CC) recombinant inbred (RI) panel (the pre-CC population) to study how genetic variation impacts influenza associated disease across a genetically diverse population. A wide range of variation in influenza disease related phenotypes including virus replication, virus-induced inflammation, and weight loss was observed. Many of the disease associated phenotypes were correlated, with viral replication and virus-induced inflammation being predictors of virus-induced weight loss. Despite these correlations, pre-CC mice with unique and novel disease phenotype combinations were observed. We also identified sets of transcripts (modules) that were correlated with aspects of disease. In order to identify how host genetic polymorphisms contribute to the observed variation in disease, we conducted quantitative trait loci (QTL) mapping. We identified several QTL contributing to specific aspects of the host response including virus-induced weight loss, titer, pulmonary edema, neutrophil recruitment to the airways, and transcriptional expression. Existing whole-genome sequence data was applied to identify high priority candidate genes within QTL regions. A key host response QTL was located at the site of the known anti-influenza Mx1 gene. We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss. PMID:23468633

Inbreeding Avoidance Drives Consistent Variation of Fine-Scale Genetic Structure Caused by Dispersal in the Seasonal Mating System of Brandt’s Voles

PubMed Central

Liu, Xiao Hui; Yue, Ling Fen; Wang, Da Wei; Li, Ning; Cong, Lin

2013-01-01

Inbreeding depression is a major evolutionary and ecological force influencing population dynamics and the evolution of inbreeding-avoidance traits such as mating systems and dispersal. Mating systems and dispersal are fundamental determinants of population genetic structure. Resolving the relationships among genetic structure, seasonal breeding-related mating systems and dispersal will facilitate our understanding of the evolution of inbreeding avoidance. The goals of this study were as follows: (i) to determine whether females actively avoided mating with relatives in a group-living rodent species, Brandt’s voles (Lasiopodomys brandtii), by combined analysis of their mating system, dispersal and genetic structure; and (ii) to analyze the relationships among the variation in fine-genetic structure, inbreeding avoidance, season-dependent mating strategies and individual dispersal. Using both individual- and population-level analyses, we found that the majority of Brandt’s vole groups consisted of close relatives. However, both group-specific FISs, an inbreeding coefficient that expresses the expected percentage rate of homozygosity arising from a given breeding system, and relatedness of mates showed no sign of inbreeding. Using group pedigrees and paternity analysis, we show that the mating system of Brandt’s voles consists of a type of polygyny for males and extra-group polyandry for females, which may decrease inbreeding by increasing the frequency of mating among distantly-related individuals. The consistent variation in within-group relatedness, among-group relatedness and fine-scale genetic structures was mostly due to dispersal, which primarily occurred during the breeding season. Biologically relevant variation in the fine-scale genetic structure suggests that dispersal during the mating season may be a strategy to avoid inbreeding and drive the polygynous and extra-group polyandrous mating system of this species. PMID:23516435

PCR/RFLP-based analysis of genetically distinct Plasmodium vivax population of Pvmsp-3α and Pvmsp-3β genes in Pakistan.

PubMed

Khan, Shahid Niaz; Khan, Asif; Khan, Sanaullah; Ayaz, Sultan; Attaullah, Sobia; Khan, Jabbar; Khan, Muhammad Asim; Ali, Ijaz; Shah, Abdul Haleem

2014-09-09

Plasmodium vivax is one of the widespread human malarial parasites accounting for 75% of malaria epidemics. However, there is no baseline information about the status and nature of genetic variation of Plasmodium species circulating in various parts of Pakistan. The present study was aimed at observing the molecular epidemiology and genetic variation of Plasmodium vivax by analysing its merozoite surface protein-3α (msp-3α) and merozoite surface protein-3β (msp-3β) genes, by using suballele, species-specific, combined nested PCR/RFLP detection techniques. A total of 230 blood samples from suspected subjects tested slide positive for vivax malaria were collected from Punjab, Sindh, Khyber Pakhtunkhwa, and Balochistan during the period May 2012 to December 2013. Combined nested PCR/RFLP technique was conducted using Pvmsp-3α and Pvmsp-3β genetic markers to detect extent of genetic variation in clinical isolates of P. vivax in the studied areas of Pakistan. By PCR, P. vivax, 202/230 (87.82%), was found to be widely distributed in the studied areas. PCR/RFLP analysis showed a high range of allelic variations for both msp-3α and msp-3β genetic markers of P. vivax, i.e., 21 alleles for msp-3α and 19 for msp-3β. Statistically a significant difference (p ≤ 0.05) was observed in the genetic diversity of the suballelic variants of msp-3α and msp-3β genes of P. vivax. It is concluded that P. vivax populations are highly polymorphic and diverse allelic variants of Pvmsp-3α and Pvmsp-3β are present in Pakistan.

Spatial and temporal variability of microgeographic genetic structure in white-tailed deer

USGS Publications Warehouse

Scribner, Kim T.; Smith, Michael H.; Chesser, Ronald K.

1997-01-01

Techniques are described that define contiguous genetic subpopulations of white-tailed deer (Odocoileus virginianus) based on the spatial dispersion of 4,749 individuals that possessed discrete character values (alleles or genotypes) during each of 6 years (1974-1979). White-tailed deer were not uniformly distributed in space, but exhibited considerable spatial genetic structuring. Significant non-random clusters of individuals were documented during each year based on specific alleles and genotypes at the Sdh locus. Considerable temporal variation was observed in the position and genetic composition of specific clusters, which reflected changes in allele frequency in small geographic areas. The position of clusters did not consistently correspond with traditional management boundaries based on major discontinuities in habitat (swamp versus upland) and hunt compartments that were defined by roads and streams. Spatio-temporal stability of observed genetic contiguous clusters was interpreted relative to method and intensity of harvest, movements, and breeding ecology.

Sex-linked inheritance of host-plant specialization in a polyphagous butterfly

PubMed Central

Janz, N.

1998-01-01

I investigated the genetic background of intraspecific variation in oviposition specificity in the generalist butterfly Polygonia c-album. Using reciprocal crosses between two populations that differ in their degree of specialization, I show that specificity is strongly sex-linked. This indicates that genes determining this difference are located primarily on the paternally inherited X-chromosome. The results suggest that intraspecific differences in specificity are caused by the same genetic mechanisms that have been shown to determine interspecific differences in host-plant ranking in other butterflies. Accordingly, the common assumption that specialization and ranking are determined by fundamentally different mechanisms was not supported.

Functional heterogeneity and heritability in CHO cell populations.

PubMed

Davies, Sarah L; Lovelady, Clare S; Grainger, Rhian K; Racher, Andrew J; Young, Robert J; James, David C

2013-01-01

In this study, we address the hypothesis that it is possible to exploit genetic/functional variation in parental Chinese hamster ovary (CHO) cell populations to isolate clonal derivatives that exhibit superior, heritable attributes for biomanufacturing--new parental cell lines which are inherently more "fit for purpose." One-hundred and ninety-nine CHOK1SV clones were isolated from a donor CHOK1SV parental population by limiting dilution cloning and microplate image analysis, followed by primary analysis of variation in cell-specific proliferation rate during extended deep-well microplate suspension culture of individual clones to accelerate genetic drift in isolated cultures. A subset of 100 clones were comparatively evaluated for transient production of a recombinant monoclonal antibody (Mab) and green fluorescent protein following transfection of a plasmid vector encoding both genes. The heritability of both cell-specific proliferation rate and Mab production was further assessed using a subset of 23 clones varying in functional capability that were subjected to cell culture regimes involving both cryopreservation and extended sub-culture. These data showed that whilst differences in transient Mab production capability were not heritable per se, clones exhibiting heritable variation in specific proliferation rate, endocytotic transfectability and N-glycan processing were identified. Finally, for clonal populations most "evolved" by extended sub-culture in vitro we investigated the relationship between cellular protein biomass content, specific proliferation rate and cell surface N-glycosylation. Rapid-specific proliferation rate was inversely correlated to CHO cell size and protein content, and positively correlated to cell surface glycan content, although substantial clone-specific variation in ability to accumulate cell biomass was evident. Taken together, our data reveal the dynamic nature of the CHO cell functional genome and the potential to evolve and isolate CHO cell variants with improved functional properties in vitro. Copyright © 2012 Wiley Periodicals, Inc.

Interactive effects of genotype and food quality on consumer growth rate and elemental content.

PubMed

Prater, Clay; Wagner, Nicole D; Frost, Paul C

2017-05-01

Consumer body stoichiometry is a key trait that links organismal physiology to population and ecosystem-level dynamics. However, as elemental composition has traditionally been considered to be constrained within a species, the ecological and evolutionary factors shaping consumer elemental composition have not been clearly resolved. To this end, we examined the causes and extent of variation in the body phosphorus (P) content and the expression of P-linked traits, mass specific growth rate (MSGR), and P use efficiency (PUE) of the keystone aquatic consumer Daphnia using lake surveys and common garden experiments. While daphnid body %P was relatively constrained in field assemblages sampled across an environmental P gradient, unique genotypes isolated from these lakes showed highly variable phenotypic responses when raised across dietary P gradients in the laboratory. Specifically, we observed substantial inter- and intra-specific variation and differences in daphnid responses within and among our study lakes. While variation in Daphnia body %P was mostly due to plastic phenotypic changes, we documented considerable genetic differences in daphnid MSGR and PUE, and relationships between MSGR and body P content were highly variable among genotypes. Overall, our study found that consumer responses to food quality may differ considerably among genotypes and that relationships between organismal life-history traits and body stoichiometry may be strongly influenced by genetic and environmental variation in natural assemblages. © 2017 by the Ecological Society of America.

Developmental origins of a novel gut morphology in frogs.

PubMed

Bloom, Stephanie; Ledon-Rettig, Cris; Infante, Carlos; Everly, Anne; Hanken, James; Nascone-Yoder, Nanette

2013-05-01

Phenotypic variation is a prerequisite for evolution by natural selection, yet the processes that give rise to the novel morphologies upon which selection acts are poorly understood. We employed a chemical genetic screen to identify developmental changes capable of generating ecologically relevant morphological variation as observed among extant species. Specifically, we assayed for exogenously applied small molecules capable of transforming the ancestral larval foregut of the herbivorous Xenopus laevis to resemble the derived larval foregut of the carnivorous Lepidobatrachus laevis. Appropriately, the small molecules that demonstrate this capacity modulate conserved morphogenetic pathways involved in gut development, including downregulation of retinoic acid (RA) signaling. Identical manipulation of RA signaling in a species that is more closely related to Lepidobatrachus, Ceratophrys cranwelli, yielded even more similar transformations, corroborating the relevance of RA signaling variation in interspecific morphological change. Finally, we were able to recover the ancestral gut phenotype in Lepidobatrachus by performing a reverse chemical manipulation to upregulate RA signaling, providing strong evidence that modifications to this specific pathway promoted the emergence of a lineage-specific phenotypic novelty. Interestingly, our screen also revealed pathways that have not yet been implicated in early gut morphogenesis, such as thyroid hormone signaling. In general, the chemical genetic screen may be a valuable tool for identifying developmental mechanisms that underlie ecologically and evolutionarily relevant phenotypic variation. © 2013 Wiley Periodicals, Inc.

Homozygosity mapping and sequencing identify two genes that might contribute to pointing behavior in hunting dogs.

PubMed

Akkad, Denis A; Gerding, Wanda M; Gasser, Robin B; Epplen, Jörg T

2015-01-01

The domestic dog represents an important model for studying the genetics of behavior. In spite of technological advances in genomics and phenomics, the genetic basis of most specific canine behaviors is largely unknown. Some breeds of hunting dogs exhibit a behavioral trait called "pointing" (a prolonged halt of movement to indicate the position of a game animal). Here, the genomes of pointing dogs (Large Munsterlander and Weimaraner) were compared with those of behaviorally distinct herding dogs (Berger des Pyrenées and Schapendoes). We assumed (i) that these four dog breeds initially represented inbred populations and (ii) that selective breeding for pointing behavior promotes an enrichment of the genetic trait in a homozygous state. The homozygosity mapping of 52 dogs (13 of each of the four breeds) followed by subsequent interval resequencing identified fixed genetic differences on chromosome 22 between pointers and herding dogs. In addition, we identified one non-synonomous variation in each of the coding genes SETDB2 and CYSLTR2 that might have a functional consequence. Genetic analysis of additional hunting and non-hunting dogs revealed consistent homozygosity for these two variations in six of seven pointing breeds. Based on the present findings, we propose that, together with other genetic, training and/or environmental factors, the nucleotide and associated amino acid variations identified in genes SETDB2 and CYSLTR2 contribute to pointing behavior.

Genetic variation facilitates seedling establishment but not population growth rate of a perennial invader.

PubMed

Li, Shou-Li; Vasemägi, Anti; Ramula, Satu

2016-01-01

Assessing the demographic consequences of genetic variation is fundamental to invasion biology. However, genetic and demographic approaches are rarely combined to explore the effects of genetic variation on invasive populations in natural environments. This study combined population genetics, demographic data and a greenhouse experiment to investigate the consequences of genetic variation for the population fitness of the perennial, invasive herb Lupinus polyphyllus. Genetic and demographic data were collected from 37 L. polyphyllus populations representing different latitudes in Finland, and genetic variation was characterized based on 13 microsatellite loci. Associations between genetic variation and population size, population density, latitude and habitat were investigated. Genetic variation was then explored in relation to four fitness components (establishment, survival, growth, fecundity) measured at the population level, and the long-term population growth rate (λ). For a subset of populations genetic variation was also examined in relation to the temporal variability of λ. A further assessment was made of the role of natural selection in the observed variation of certain fitness components among populations under greenhouse conditions. It was found that genetic variation correlated positively with population size, particularly at higher latitudes, and differed among habitat types. Average seedling establishment per population increased with genetic variation in the field, but not under greenhouse conditions. Quantitative genetic divergence (Q(ST)) based on seedling establishment in the greenhouse was smaller than allelic genetic divergence (F'(ST)), indicating that unifying selection has a prominent role in this fitness component. Genetic variation was not associated with average survival, growth or fecundity measured at the population level, λ or its variability. The study suggests that although genetic variation may facilitate plant invasions by increasing seedling establishment, it may not necessarily affect the long-term population growth rate. Therefore, established invasions may be able to grow equally well regardless of their genetic diversity. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The alignment between phenotypic plasticity, the major axis of genetic variation and the response to selection.

PubMed

Lind, Martin I; Yarlett, Kylie; Reger, Julia; Carter, Mauricio J; Beckerman, Andrew P

2015-10-07

Phenotypic plasticity is the ability of a genotype to produce more than one phenotype in order to match the environment. Recent theory proposes that the major axis of genetic variation in a phenotypically plastic population can align with the direction of selection. Therefore, theory predicts that plasticity directly aids adaptation by increasing genetic variation in the direction favoured by selection and reflected in plasticity. We evaluated this theory in the freshwater crustacean Daphnia pulex, facing predation risk from two contrasting size-selective predators. We estimated plasticity in several life-history traits, the G matrix of these traits, the selection gradients on reproduction and survival, and the predicted responses to selection. Using these data, we tested whether the genetic lines of least resistance and the predicted response to selection aligned with plasticity. We found predator environment-specific G matrices, but shared genetic architecture across environments resulted in more constraint in the G matrix than in the plasticity of the traits, sometimes preventing alignment of the two. However, as the importance of survival selection increased, the difference between environments in their predicted response to selection increased and resulted in closer alignment between the plasticity and the predicted selection response. Therefore, plasticity may indeed aid adaptation to new environments. © 2015 The Authors.

Large-scale analysis of pedigree and sperm-typing data reveals PRDM9 allele-specific recombination maps in cattle

USDA-ARS?s Scientific Manuscript database

Meiotic recombination is a major driving force in promoting genetic and phenotypic variations in sexually reproducing organisms. Although PRDM9 is known to modulate the binding-specificity and location of recombination hotspots in humans and mice, its role, especially in domesticated animals like ca...

Whole genome sequencing of Turkish genomes reveals functional private alleles and impact of genetic interactions with Europe, Asia and Africa.

PubMed

Alkan, Can; Kavak, Pinar; Somel, Mehmet; Gokcumen, Omer; Ugurlu, Serkan; Saygi, Ceren; Dal, Elif; Bugra, Kuyas; Güngör, Tunga; Sahinalp, S Cenk; Özören, Nesrin; Bekpen, Cemalettin

2014-11-07

Turkey is a crossroads of major population movements throughout history and has been a hotspot of cultural interactions. Several studies have investigated the complex population history of Turkey through a limited set of genetic markers. However, to date, there have been no studies to assess the genetic variation at the whole genome level using whole genome sequencing. Here, we present whole genome sequences of 16 Turkish individuals resequenced at high coverage (32×-48×). We show that the genetic variation of the contemporary Turkish population clusters with South European populations, as expected, but also shows signatures of relatively recent contribution from ancestral East Asian populations. In addition, we document a significant enrichment of non-synonymous private alleles, consistent with recent observations in European populations. A number of variants associated with skin color and total cholesterol levels show frequency differentiation between the Turkish populations and European populations. Furthermore, we have analyzed the 17q21.31 inversion polymorphism region (MAPT locus) and found increased allele frequency of 31.25% for H1/H2 inversion polymorphism when compared to European populations that show about 25% of allele frequency. This study provides the first map of common genetic variation from 16 western Asian individuals and thus helps fill an important geographical gap in analyzing natural human variation and human migration. Our data will help develop population-specific experimental designs for studies investigating disease associations and demographic history in Turkey.

GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics

PubMed Central

Ledda, Mirko; Kutalik, Zoltán; Souza Destito, Maria C.; Souza, Milena M.; Cirillo, Cintia A.; Zamboni, Amabilene; Martin, Nathalie; Morya, Edgard; Sameshima, Koichi; Beckmann, Jacques S.; le Coutre, Johannes; Bergmann, Sven; Genick, Ulrich K.

2014-01-01

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88– 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10−13, r2 = 8.9%, β = −0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with—but is statistically distinct from—the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10−37, r2 = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perception. PMID:23966204

Global and disease-associated genetic variation in the human Fanconi anemia gene family.

PubMed

Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

2014-12-20

Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Recent advances in understanding the role of nutrition in human genome evolution.

PubMed

Ye, Kaixiong; Gu, Zhenglong

2011-11-01

Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics.

A Genome Wide Survey of SNP Variation Reveals the Genetic Structure of Sheep Breeds

PubMed Central

Kijas, James W.; Townley, David; Dalrymple, Brian P.; Heaton, Michael P.; Maddox, Jillian F.; McGrath, Annette; Wilson, Peter; Ingersoll, Roxann G.; McCulloch, Russell; McWilliam, Sean; Tang, Dave; McEwan, John; Cockett, Noelle; Oddy, V. Hutton; Nicholas, Frank W.; Raadsma, Herman

2009-01-01

The genetic structure of sheep reflects their domestication and subsequent formation into discrete breeds. Understanding genetic structure is essential for achieving genetic improvement through genome-wide association studies, genomic selection and the dissection of quantitative traits. After identifying the first genome-wide set of SNP for sheep, we report on levels of genetic variability both within and between a diverse sample of ovine populations. Then, using cluster analysis and the partitioning of genetic variation, we demonstrate sheep are characterised by weak phylogeographic structure, overlapping genetic similarity and generally low differentiation which is consistent with their short evolutionary history. The degree of population substructure was, however, sufficient to cluster individuals based on geographic origin and known breed history. Specifically, African and Asian populations clustered separately from breeds of European origin sampled from Australia, New Zealand, Europe and North America. Furthermore, we demonstrate the presence of stratification within some, but not all, ovine breeds. The results emphasize that careful documentation of genetic structure will be an essential prerequisite when mapping the genetic basis of complex traits. Furthermore, the identification of a subset of SNP able to assign individuals into broad groupings demonstrates even a small panel of markers may be suitable for applications such as traceability. PMID:19270757

Implications of sex-specific selection for the genetic basis of disease.

PubMed

Morrow, Edward H; Connallon, Tim

2013-12-01

Mutation and selection are thought to shape the underlying genetic basis of many common human diseases. However, both processes depend on the context in which they occur, such as environment, genetic background, or sex. Sex has widely known effects on phenotypic expression of genotype, but an analysis of how it influences the evolutionary dynamics of disease-causing variants has not yet been explored. We develop a simple population genetic model of disease susceptibility and evaluate it using a biologically plausible empirically based distribution of fitness effects among contributing mutations. The model predicts that alleles under sex-differential selection, including sexually antagonistic alleles, will disproportionately contribute to genetic variation for disease predisposition, thereby generating substantial sexual dimorphism in the genetic architecture of complex (polygenic) diseases. This is because such alleles evolve into higher population frequencies for a given effect size, relative to alleles experiencing equally strong purifying selection in both sexes. Our results provide a theoretical justification for expecting a sexually dimorphic genetic basis for variation in complex traits such as disease. Moreover, they suggest that such dimorphism is interesting - not merely something to control for - because it reflects the action of natural selection in molding the evolution of common disease phenotypes.

Copy number analysis reveals a novel multiexon deletion of the COLQ gene in congenital myasthenia.

PubMed

Wang, Wei; Wu, Yanhong; Wang, Chen; Jiao, Jinsong; Klein, Christopher J

2016-12-01

Congenital myasthenic syndrome (CMS) is genetically and clinically heterogeneous. 1 Despite a considerable number of causal genes discovered, many patients are left without a specific diagnosis after genetic testing. The presumption is that novel genes yet to be discovered will account for the majority of such patients. However, it is also possible that we are neglecting a type of genetic variation: copy number changes (>50 bp) as causal for some of these patients. Next-generation sequencing (NGS) can simultaneously screen all known causal genes 2 and is increasingly being validated to have a potential to identify copy number changes. 3 We present a CMS case who did not receive a genetic diagnosis from previous Sanger sequencing, but through a novel copy number analysis algorithm integrated into our targeted NGS panel, we discovered a novel copy number mutation in the COLQ gene and made a genetic diagnosis. This discovery expands the genotype-phenotype correlation of CMS, leads to improved genetic counsel, and allows for specific pharmacologic treatment. 1 .

Maternal genetic effects on adaptive divergence between anadromous and resident brook charr during early life history.

PubMed

Perry, G M L; Audet, C; Bernatchez, L

2005-09-01

The importance of directional selection relative to neutral evolution may be determined by comparing quantitative genetic variation in phenotype (Q(ST)) to variation at neutral molecular markers (F(ST)). Quantitative divergence between salmonid life history types is often considerable, but ontogenetic changes in the significance of major sources of genetic variance during post-hatch development suggest that selective differentiation varies by developmental stage. In this study, we tested the hypothesis that maternal genetic differentiation between anadromous and resident brook charr (Salvelinus fontinalis Mitchill) populations for early quantitative traits (embryonic size/growth, survival, egg number and developmental time) would be greater than neutral genetic differentiation, but that the maternal genetic basis for differentiation would be higher for pre-resorption traits than post-resorption traits. Quantitative genetic divergence between anadromous (seawater migratory) and resident Laval River (Québec) brook charr based on maternal genetic variance was high (Q(ST) > 0.4) for embryonic length, yolk sac volume, embryonic growth rate and time to first response to feeding relative to neutral genetic differentiation [F(ST) = 0.153 (0.071-0.214)], with anadromous females having positive genetic coefficients for all of the above characters. However, Q(ST) was essentially zero for all traits post-resorption of the yolk sac. Our results indicate that the observed divergence between resident and anadromous brook charr has been driven by directional selection, and may therefore be adaptive. Moreover, they provide among the first evidence that the relative importance of selective differentiation may be highly context-specific, and varies by genetic contributions to phenotype by parental sex at specific points in offspring ontogeny. This in turn suggests that interpretations of Q(ST)-F(ST) comparisons may be improved by considering the structure of quantitative genetic architecture by age category and the sex of the parent used in estimation.

Genetic and Environmental Influences on the Developmental Course of Attention-Deficit/Hyperactivity Disorder Symptoms From Childhood to Adolescence.

PubMed

Pingault, Jean-Baptiste; Viding, Essi; Galéra, Cédric; Greven, Corina U; Zheng, Yao; Plomin, Robert; Rijsdijk, Frühling

2015-07-01

Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as a neurodevelopmental disorder that is strongly heritable. However, to our knowledge, no study to date has examined the genetic and environmental influences explaining interindividual differences in the developmental course of ADHD symptoms from childhood to adolescence (ie, systematic decreases or increases with age). The reason ADHD symptoms persist in some children but decline in others is an important concern, with implications for prognosis and interventions. To assess the proportional impact of genes and the environment on interindividual differences in the developmental course of ADHD symptom domains of hyperactivity/impulsivity and inattention between ages 8 and 16 years. A prospective sample of 8395 twin pairs from the Twins Early Development Study, recruited from population records of births in England and Wales between January 1, 1994, and December 31, 1996. Data collection at age 8 years took place between November 2002 and November 2004; data collection at age 16 years took place between February 2011 and January 2013. Both DSM-IV ADHD symptom subscales were rated 4 times by participants' mothers. Estimates from latent growth curve models indicated that the developmental course of hyperactivity/impulsivity symptoms followed a sharp linear decrease (mean score of 6.0 at age 8 years to 2.9 at age 16 years). Interindividual differences in the linear change in hyperactivity/impulsivity were under strong additive genetic influences (81%; 95% CI, 73%-88%). More than half of the genetic variation was specific to the developmental course and not shared with the baseline level of hyperactivity/impulsivity. The linear decrease in inattention symptoms was less pronounced (mean score of 5.8 at age 8 years to 4.9 at age 16 years). Nonadditive genetic influences accounted for a substantial amount of variation in the developmental course of inattention symptoms (54%; 95% CI, 8%-76%), with more than half being specific to the developmental course. The large genetic influences on the developmental course of ADHD symptoms are mostly specific and independent of those that account for variation in the baseline level of symptoms. Different sets of genes may be associated with the developmental course vs the baseline level of ADHD symptoms and explain why some children remit from ADHD, whereas others persist. Recent longitudinal imaging data indicate that the maintenance or increase in symptoms is underpinned by atypical trajectories of cortical development. This may reflect a specific genetic liability, distinct from that which contributes to baseline ADHD symptoms, and warrants closer follow-up.

Practical guidelines addressing ethical issues pertaining to the curation of human locus-specific variation databases (LSDBs)

PubMed Central

Povey, Sue; Al Aqeel, Aida I; Cambon-Thomsen, Anne; Dalgleish, Raymond; den Dunnen, Johan T; Firth, Helen V; Greenblatt, Marc S; Barash, Carol Isaacson; Parker, Michael; Patrinos, George P; Savige, Judith; Sobrido, Maria-Jesus; Winship, Ingrid; Cotton, Richard GH

2010-01-01

More than 1,000 Web-based locus-specific variation databases (LSDBs) are listed on the Website of the Human Genetic Variation Society (HGVS). These individual efforts, which often relate phenotype to genotype, are a valuable source of information for clinicians, patients, and their families, as well as for basic research. The initiators of the Human Variome Project recently recognized that having access to some of the immense resources of unpublished information already present in diagnostic laboratories would provide critical data to help manage genetic disorders. However, there are significant ethical issues involved in sharing these data worldwide. An international working group presents second-generation guidelines addressing ethical issues relating to the curation of human LSDBs that provide information via a Web-based interface. It is intended that these should help current and future curators and may also inform the future decisions of ethics committees and legislators. These guidelines have been reviewed by the Ethics Committee of the Human Genome Organization (HUGO). Hum Mutat 31:–6, 2010. © 2010 Wiley-Liss, Inc. PMID:20683926

Habitat-specific population structure in native western flower thrips Frankliniella occidentalis (Insecta, Thysanoptera).

PubMed

Brunner, P C; Frey, J E

2010-04-01

Invasions by pest organisms are among the main challenges for sustainable crop protection. They pose a serious threat to crop production by introducing a highly unpredictable element to existing crop protection strategies. The western flower thrips Frankliniella occidentalis (Insecta, Thysanoptera) managed to invade ornamental greenhouses worldwide within < 25 years. To shed light on possible genetic and/or ecological factors that may have been responsible for this invasion success, we studied the population genetic structure of western flower thrips in its native range in western North America. Analysis of nucleotide sequence variation and variation at microsatellite loci revealed the existence of two habitat-specific phylogenetic lineages (ecotypes) with allopatric distribution. One lineage is associated with hot/dry climates, the second lineage is restricted to cool/moist climates. We speculate that the ecological niche segregation found in this study may be among the key factors determining the invasion potential of western flower thrips.

Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

PubMed Central

Gupta, Vinod K.; Paul, Sandip; Dutta, Chitra

2017-01-01

One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT). The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics or his environment. Some of the geographical/racial variations in microbiome structure have been attributed to differences in host genetics and innate/adaptive immunity, while in many other cases, cultural/behavioral features like diet, hygiene, parasitic load, environmental exposure etc. overshadow genetics. The ethnicity or population-specific variations in human microbiome composition, as reviewed in this report, question the universality of the microbiome-based therapeutic strategies and recommend for geographically tailored community-scale approaches to microbiome engineering. PMID:28690602

Wild worm embryogenesis harbors ubiquitous polygenic modifier variation.

PubMed

Paaby, Annalise B; White, Amelia G; Riccardi, David D; Gunsalus, Kristin C; Piano, Fabio; Rockman, Matthew V

2015-08-22

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture.

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

PubMed

Petry, Clive J; Rayco-Solon, Pura; Fulford, Anthony J C; Stead, John D H; Wingate, Dianne L; Ong, Ken K; Sirugo, Giorgio; Prentice, Andrew M; Dunger, David B

2009-09-01

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.

Metabolite profiling and quantitative genetics of natural variation for flavonoids in Arabidopsis

PubMed Central

Routaboul, Jean-Marc; Dubos, Christian; Beck, Gilles; Marquis, Catherine; Bidzinski, Przemyslaw; Loudet, Olivier; Lepiniec, Loïc

2012-01-01

Little is known about the range and the genetic bases of naturally occurring variation for flavonoids. Using Arabidopsis thaliana seed as a model, the flavonoid content of 41 accessions and two recombinant inbred line (RIL) sets derived from divergent accessions (Cvi-0×Col-0 and Bay-0×Shahdara) were analysed. These accessions and RILs showed mainly quantitative rather than qualitative changes. To dissect the genetic architecture underlying these differences, a quantitative trait locus (QTL) analysis was performed on the two segregating populations. Twenty-two flavonoid QTLs were detected that accounted for 11–64% of the observed trait variations, only one QTL being common to both RIL sets. Sixteen of these QTLs were confirmed and coarsely mapped using heterogeneous inbred families (HIFs). Three genes, namely TRANSPARENT TESTA (TT)7, TT15, and MYB12, were proposed to underlie their variations since the corresponding mutants and QTLs displayed similar specific flavonoid changes. Interestingly, most loci did not co-localize with any gene known to be involved in flavonoid metabolism. This latter result shows that novel functions have yet to be characterized and paves the way for their isolation. PMID:22442426

Genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains.

PubMed

Lee, Kang-Hoon; Lim, Debora; Chiu, Sophia; Greenhalgh, David; Cho, Kiho

2016-04-01

Laboratory strains of mice, both conventional and genetically engineered, have been introduced as critical components of a broad range of studies investigating normal and disease biology. Currently, the genetic identity of laboratory mice is primarily confirmed by surveying polymorphisms in selected sets of "conventional" genes and/or microsatellites in the absence of a single completely sequenced mouse genome. First, we examined variations in the genomic landscapes of transposable repetitive elements, named the TREome, in conventional and genetically engineered mouse strains using murine leukemia virus-type endogenous retroviruses (MLV-ERVs) as a probe. A survey of the genomes from 56 conventional strains revealed strain-specific TREome landscapes, and certain families (e.g., C57BL) of strains were discernible with defined patterns. Interestingly, the TREome landscapes of C3H/HeJ (toll-like receptor-4 [TLR4] mutant) inbred mice were different from its control C3H/HeOuJ (TLR4 wild-type) strain. In addition, a CD14 knock-out strain had a distinct TREome landscape compared to its control/backcross C57BL/6J strain. Second, an examination of superantigen (SAg, a "TREome gene") coding sequences of mouse mammary tumor virus-type ERVs in the genomes of the 46 conventional strains revealed a high diversity, suggesting a potential role of SAgs in strain-specific immune phenotypes. The findings from this study indicate that unexplored and intricate genomic variations exist in laboratory mouse strains, both conventional and genetically engineered. The TREome-based high-resolution genetics surveillance system for laboratory mice would contribute to efficient study design with quality control and accurate data interpretation. This genetics system can be easily adapted to other species ranging from plants to humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantitative Resistance: More Than Just Perception of a Pathogen.

PubMed

Corwin, Jason A; Kliebenstein, Daniel J

2017-04-01

Molecular plant pathology has focused on studying large-effect qualitative resistance loci that predominantly function in detecting pathogens and/or transmitting signals resulting from pathogen detection. By contrast, less is known about quantitative resistance loci, particularly the molecular mechanisms controlling variation in quantitative resistance. Recent studies have provided insight into these mechanisms, showing that genetic variation at hundreds of causal genes may underpin quantitative resistance. Loci controlling quantitative resistance contain some of the same causal genes that mediate qualitative resistance, but the predominant mechanisms of quantitative resistance extend beyond pathogen recognition. Indeed, most causal genes for quantitative resistance encode specific defense-related outputs such as strengthening of the cell wall or defense compound biosynthesis. Extending previous work on qualitative resistance to focus on the mechanisms of quantitative resistance, such as the link between perception of microbe-associated molecular patterns and growth, has shown that the mechanisms underlying these defense outputs are also highly polygenic. Studies that include genetic variation in the pathogen have begun to highlight a potential need to rethink how the field considers broad-spectrum resistance and how it is affected by genetic variation within pathogen species and between pathogen species. These studies are broadening our understanding of quantitative resistance and highlighting the potentially vast scale of the genetic basis of quantitative resistance. © 2017 American Society of Plant Biologists. All rights reserved.

Genetic susceptibility to type 2 diabetes and obesity: follow-up of findings from genome-wide association studies.

PubMed

Basile, Kevin J; Johnson, Matthew E; Xia, Qianghua; Grant, Struan F A

2014-01-01

Elucidating the underlying genetic variations influencing various complex diseases is one of the major challenges currently facing clinical genetic research. Although these variations are often difficult to uncover, approaches such as genome-wide association studies (GWASs) have been successful at finding statistically significant associations between specific genomic loci and disease susceptibility. GWAS has been especially successful in elucidating genetic variants that influence type 2 diabetes (T2D) and obesity/body mass index (BMI). Specifically, several GWASs have confirmed that a variant in transcription factor 7-like 2 (TCF7L2) confers risk for T2D, while a variant in fat mass and obesity-associated protein (FTO) confers risk for obesity/BMI; indeed both of these signals are considered the most statistically associated loci discovered for these respective traits to date. The discovery of these two key loci in this context has been invaluable for providing novel insight into mechanisms of heritability and disease pathogenesis. As follow-up studies of TCF7L2 and FTO have typically lead the way in how to follow up a GWAS discovery, we outline what has been learned from such investigations and how they have implications for the myriad of other loci that have been subsequently reported in this disease context.

The humankind genome: from genetic diversity to the origin of human diseases.

PubMed

Belizário, Jose E

2013-12-01

Genome-wide association studies have failed to establish common variant risk for the majority of common human diseases. The underlying reasons for this failure are explained by recent studies of resequencing and comparison of over 1200 human genomes and 10 000 exomes, together with the delineation of DNA methylation patterns (epigenome) and full characterization of coding and noncoding RNAs (transcriptome) being transcribed. These studies have provided the most comprehensive catalogues of functional elements and genetic variants that are now available for global integrative analysis and experimental validation in prospective cohort studies. With these datasets, researchers will have unparalleled opportunities for the alignment, mining, and testing of hypotheses for the roles of specific genetic variants, including copy number variations, single nucleotide polymorphisms, and indels as the cause of specific phenotypes and diseases. Through the use of next-generation sequencing technologies for genotyping and standardized ontological annotation to systematically analyze the effects of genomic variation on humans and model organism phenotypes, we will be able to find candidate genes and new clues for disease's etiology and treatment. This article describes essential concepts in genetics and genomic technologies as well as the emerging computational framework to comprehensively search websites and platforms available for the analysis and interpretation of genomic data.

Comparing intra- and inter-specific effects on litter decomposition in an old-field ecosystem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crutsinger, Greg; Sanders, Dr. Nathan James; Classen, Aimee T

2009-09-01

Plant species can differ in the quantity and quality of leaf litter they produce, and many studies have examined whether plant species diversity affects leaf-litter decomposition and nutrient release. A growing number of studies have indicated that intra-specific variation within plant species can also affect key ecosystem processes. However, the relative importance of intra- versus inter-specific variation for the functioning of ecosystems remains poorly known. Here, we investigate the effects of intra-specific variation in a dominant old-field plant species, tall goldenrod (Solidago altissima), and inter-specific variation among goldenrod species on litter quality, decomposition, and nitrogen (N) release. We found thatmore » the nutrient concentration of leaf litter varied among genotypes, which translated into 50% difference in decomposition rates. Variation among other goldenrod species in decomposition rate was more than twice that of genetic variation within S. altissima. Furthermore, by manipulating litterbags to contain 1, 3, 6, or 9 genotypes, we found that S. altissima genotype identity had much stronger effects than did genotypic diversity on leaf-litter quality, decomposition, and N release. Taken together, these results suggest that the order of ecological importance for controlling leaf-litter decomposition and N release dynamics is plant species identitygenotype identity>genotypic diversity.« less

Effects of population succession on demographic and genetic processes: predictions and tests in the daylily Hemerocallis thunbergii (Liliaceae).

PubMed

Chung, Mi Yoon; Nason, John D; Chung, Myong Gi

2007-07-01

Spatial genetic structure within plant populations is influenced by variation in demographic processes through space and time, including a population's successional status. To determine how demographic structure and fine-scale genetic structure (FSGS) change with stages in a population's successional history, we studied Hemerocallis thunbergii (Liliaceae), a nocturnal flowering and hawkmoth-pollinated herbaceous perennial with rapid population turnover dynamics. We examined nine populations assigned to three successive stages of population succession: expansion, maturation, and senescence. We developed stage-specific expectations for within-population demographic and genetic structure, and then for each population quantified the spatial aggregation of individuals and genotypes using spatial autocorrelation methods (nonaccumulative O-ring and kinship statistics, respectively), and at the landscape level measured inbreeding and genetic structure using Wright's F-statistics. Analyses using the O-ring statistic revealed significant aggregation of individuals at short spatial scales in expanding and senescing populations, in particular, which may reflect restricted seed dispersal around maternal individuals combined with relatively low local population densities at these stages. Significant FSGS was found for three of four expanding, no mature, and only one senescing population, a pattern generally consistent with expectations of successional processes. Although allozyme genetic diversity was high within populations (mean %P = 78.9 and H(E) = 0.281), landscape-level differentiation among sites was also high (F(ST) = 0.166) and all populations exhibited a significant deficit of heterozygotes relative to Hardy-Weinberg expectations (range F = 0.201-0.424, mean F(IS) = 0.321). Within populations, F was not correlated with the degree of FSGS, thus suggesting inbreeding due primarily to selfing as opposed to mating among close relatives in spatially structured populations. Our results demonstrate considerable variation in the spatial distribution of individuals and patterns and magnitude of FSGS in H. thunbergii populations across the landscape. This variation is generally consistent with succession-stage-specific differences in ecological processes operating within these populations.

Genetic variation in arthropod vectors of disease-causing organisms: obstacles and opportunities.

PubMed Central

Gooding, R H

1996-01-01

An overview of the genetic variation in arthropods that transmit pathogens to vertebrates is presented, emphasizing the genetics of vector-pathogen relationships and the biochemical genetics of vectors. Vector-pathogen interactions are reviewed briefly as a prelude to a discussion of the genetics of susceptibility and refractoriness in vectors. Susceptibility to pathogens is controlled by maternally inherited factors, sex-linked dominant alleles, and dominant and recessive autosomal genes. There is widespread interpopulation (including intercolony) and temporal variation in susceptibility to pathogens. The amount of biochemical genetic variation in vectors is similar to that found in other invertebrates. However, the amount varies widely among species, among populations within species, and temporally within populations. Biochemical genetic studies show that there is considerable genetic structuring of many vectors at the local, regional, and global levels. It is argued that genetic variation in vectors is critical in understanding vector-pathogen interactions and that genetic variation in vectors creates both obstacles to and opportunities for application of genetic techniques to the control of vectors. PMID:8809462

Characterization of QKI gene expression, genetics, and epigenetics in suicide victims with major depressive disorder.

PubMed

Klempan, Timothy A; Ernst, Carl; Deleva, Vesselina; Labonte, Benoit; Turecki, Gustavo

2009-11-01

A number of studies have suggested deficits in myelination and glial gene expression in different psychiatric disorders. We examined the brain expression and genetic/epigenetic regulation of QKI, an oligodendrocyte-specific RNA binding protein important for cell development and myelination. The microarray-based expression of QKI was evaluated in cortical and subcortical brain regions from suicide victims with a diagnosis of major depression (n = 16) and control subjects (n = 13). These findings were also assessed with a real-time (quantitative polymerase chain reaction [qPCR]) approach, with QKI protein levels evaluated through immunoblotting. Identification of a QKI promoter sequence was then used to examine genetic and epigenetic variation at the QKI locus. The messenger RNA (mRNA) levels of multiple transcripts of QKI were evaluated on Affymetrix microarrays, revealing significant reductions in 11 cortical regions and the hippocampus and amygdala of suicide victims compared with control subjects. Microarray findings were confirmed by qPCR, and reduced expression of QKI protein was identified in orbitofrontal cortex. Analysis of promoter variation and methylation state in a subset of individuals did not identify differences at the genetic or epigenetic level between depressed suicide victims and control subjects. The observation of consistent reductions in multiple isoforms of QKI mRNA in depressed suicide victims supports the growing body of evidence for a role of myelination-related deficits in the etiology of psychiatric disorders. A specific role of QKI in this process is implied by its reduced expression and known interactions with genes involved in oligodendrocyte determination; however, QKI gene variation responsible for these changes remains to be identified.

al mena: a comprehensive resource of human genetic variants integrating genomes and exomes from Arab, Middle Eastern and North African populations.

PubMed

Koshy, Remya; Ranawat, Anop; Scaria, Vinod

2017-10-01

Middle East and North Africa (MENA) encompass very unique populations, with a rich history and encompasses characteristic ethnic, linguistic and genetic diversity. The genetic diversity of MENA region has been largely unknown. The recent availability of whole-exome and whole-genome sequences from the region has made it possible to collect population-specific allele frequencies. The integration of data sets from this region would provide insights into the landscape of genetic variants in this region. We integrated genetic variants from multiple data sets systematically, available from this region to create a compendium of over 26 million genetic variations. The variants were systematically annotated and their allele frequencies in the data sets were computed and available as a web interface which enables quick query. As a proof of principle for application of the compendium for genetic epidemiology, we analyzed the allele frequencies for variants in transglutaminase 1 (TGM1) gene, associated with autosomal recessive lamellar ichthyosis. Our analysis revealed that the carrier frequency of selected variants differed widely with significant interethnic differences. To the best of our knowledge, al mena is the first and most comprehensive repertoire of genetic variations from the Arab, Middle Eastern and North African region. We hope al mena would accelerate Precision Medicine in the region.

Extreme mitochondrial variation in the Atlantic gall crab Opecarcinus hypostegus (Decapoda: Cryptochiridae) reveals adaptive genetic divergence over Agaricia coral hosts

PubMed Central

van Tienderen, Kaj M.; van der Meij, Sancia E. T.

2017-01-01

The effectiveness of migration in marine species exhibiting a pelagic larval stage is determined by various factors, such as ocean currents, pelagic larval stage duration and active habitat selection. Direct measurement of larval movements is difficult and, consequently, factors determining the gene flow patterns remain poorly understood for many species. Patterns of gene flow play a key role in maintaining genetic homogeneity in a species by dampening the effects of local adaptation. Coral-dwelling gall crabs (Cryptochiridae) are obligate symbionts of stony corals (Scleractinia). Preliminary data showed high genetic diversity on the COI gene for 19 Opecarcinus hypostegus specimens collected off Curaçao. In this study, an additional 176 specimens were sequenced and used to characterize the population structure along the leeward side of Curaçao. Extremely high COI genetic variation was observed, with 146 polymorphic sites and 187 unique haplotypes. To determine the cause of this high genetic diversity, various gene flow scenarios (geographical distance along the coast, genetic partitioning over depth, and genetic differentiation by coral host) were examined. Adaptive genetic divergence across Agariciidae host species is suggested to be the main cause for the observed high intra-specific variance, hypothesised as early signs of speciation in O. hypostegus. PMID:28079106

Characterization of the genetic variation present in CYP3A4 in three South African populations.

PubMed

Drögemöller, Britt; Plummer, Marieth; Korkie, Lundi; Agenbag, Gloudi; Dunaiski, Anke; Niehaus, Dana; Koen, Liezl; Gebhardt, Stefan; Schneider, Nicol; Olckers, Antonel; Wright, Galen; Warnich, Louise

2013-01-01

The CYP3A4 enzyme is the most abundant human cytochrome P450 (CYP) and is regarded as the most important enzyme involved in drug metabolism. Inter-individual and inter-population variability in gene expression and enzyme activity are thought to be influenced, in part, by genetic variation. Although Southern African individuals have been shown to exhibit the highest levels of genetic diversity, they have been under-represented in pharmacogenetic research to date. Therefore, the aim of this study was to identify genetic variation within CYP3A4 in three South African population groups comprising of 29 Khoisan, 65 Xhosa and 65 Mixed Ancestry (MA) individuals. To identify known and novel CYP3A4 variants, 15 individuals were randomly selected from each of the population groups for bi-directional Sanger sequencing of ~600 bp of the 5'-upstream region and all thirteen exons including flanking intronic regions. Genetic variants detected were genotyped in the rest of the cohort. In total, 24 SNPs were detected, including CYP3A4(*)12, CYP3A4(*)15, and the reportedly functional CYP3A4(*)1B promoter polymorphism, as well as two novel non-synonymous variants. These putatively functional variants, p.R162W and p.Q200H, were present in two of the three populations and all three populations, respectively, and in silico analysis predicted that the former would damage the protein product. Furthermore, the three populations were shown to exhibit distinct genetic profiles. These results confirm that South African populations show unique patterns of variation in the genes encoding xenobiotic metabolizing enzymes. This research suggests that population-specific genetic profiles for CYP3A4 and other drug metabolizing genes would be essential to make full use of pharmacogenetics in Southern Africa. Further investigation is needed to determine if the identified genetic variants influence CYP3A4 metabolism phenotype in these populations.

Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test.

PubMed

Atroosh, Wahib M; Al-Mekhlafi, Hesham M; Al-Jasari, Adel; Sady, Hany; Al-Delaimy, Ahmed K; Nasr, Nabil A; Dawaki, Salwa; Abdulsalam, Awatif M; Ithoi, Init; Lau, Yee Ling; Fong, Mun Yik; Surin, Johari

2015-07-22

The genetic variation in the Plasmodium falciparum histidine-rich protein 2 (pfhrp2) gene that may compromise the use of pfhrp2-based rapid diagnostic tests (RDTs) for the diagnosis of malaria was assessed in P. falciparum isolates from Yemen. This study was conducted in Hodeidah and Al-Mahwit governorates, Yemen. A total of 622 individuals with fever were examined for malaria by CareStart malaria HRP2-RDT and Giemsa-stained thin and thick blood films. The Pfhrp2 gene was amplified and sequenced from 180 isolates, and subjected to amino acid repeat types analysis. A total of 188 (30.2%) participants were found positive for P. falciparum by the RDT. Overall, 12 different amino acid repeat types were identified in Yemeni isolates. Six repeat types were detected in all the isolates (100%) namely types 1, 2, 6, 7, 10 and 12 while types 9 and 11 were not detected in any of the isolates. Moreover, the sensitivity and specificity of the used PfHRP2-based RDTs were high (90.5% and 96.1%, respectively). The present study provides data on the genetic variation within the pfhrp2 gene, and its potential impact on the PfHRP2-based RDTs commonly used in Yemen. CareStart Malaria HRP2-based RDT showed high sensitivity and specificity in endemic areas of Yemen.

Efforts to make and apply humanized yeast

PubMed Central

Laurent, Jon M.; Young, Jonathan H.; Kachroo, Aashiq H.

2016-01-01

Despite a billion years of divergent evolution, the baker’s yeast Saccharomyces cerevisiae has long proven to be an invaluable model organism for studying human biology. Given its tractability and ease of genetic manipulation, along with extensive genetic conservation with humans, it is perhaps no surprise that researchers have been able to expand its utility by expressing human proteins in yeast, or by humanizing specific yeast amino acids, proteins or even entire pathways. These methods are increasingly being scaled in throughput, further enabling the detailed investigation of human biology and disease-specific variations of human genes in a simplified model organism. PMID:26462863

Genetic variation, phenotypic stability, and repeatability of drought response in European larch throughout 50 years in a common garden experiment

PubMed Central

George, Jan-Peter; Grabner, Michael; Karanitsch-Ackerl, Sandra; Mayer, Konrad; Weißenbacher, Lambert; Schueler, Silvio

2017-01-01

Abstract Assessing intra-specific variation in drought stress response is required to mitigate the consequences of climate change on forest ecosystems. Previous studies suggest that European larch (Larix decidua Mill.), an important European conifer in mountainous and alpine forests, is highly vulnerable to drought. In light of this, we estimated the genetic variation in drought sensitivity and its degree of genetic determination in a 50-year-old common garden experiment in the drought-prone northeastern Austria. Tree ring data from larch provenances originating from across the species' natural range were used to estimate the drought reaction in four consecutive drought events (1977, 1981, 1990–1994, and 2003) with extremely low standardized precipitation- and evapotranspiration-index values that affected growth in all provenances. We found significant differences among provenances across the four drought periods for the trees’ capacity to withstand drought (resistance) and for their capacity to reach pre-drought growth levels after drought (resilience). Provenances from the species' northern distribution limit in the Polish lowlands were found to be more drought resistant and showed higher stability across all drought periods than provenances from mountainous habitats at the southern fringe. The degree of genetic determination, as estimated by the repeatability, ranged up to 0.39, but significantly differed among provenances, indicating varying degrees of natural selection at the provenance origin. Generally, the relationship between the provenances’ source climate and drought behavior was weak, suggesting that the contrasting patterns of drought response are a result of both genetic divergence out of different refugial lineages and local adaptation to summer or winter drought conditions. Our analysis suggests that European larch posseses high genetic variation among and within provenances that can be used for assisted migration and breeding programs. PMID:28173601

Behavioural response to combined insecticide and temperature stress in natural populations of Drosophila melanogaster.

PubMed

Fournier-Level, A; Neumann-Mondlak, A; Good, R T; Green, L M; Schmidt, J M; Robin, C

2016-05-01

Insecticide resistance evolves extremely rapidly, providing an illuminating model for the study of adaptation. With climate change reshaping species distribution, pest and disease vector control needs rethinking to include the effects of environmental variation and insect stress physiology. Here, we assessed how both long-term adaptation of populations to temperature and immediate temperature variation affect the genetic architecture of DDT insecticide response in Drosophila melanogaster. Mortality assays and behavioural assays based on continuous activity monitoring were used to assess the interaction between DDT and temperature on three field-derived populations from climate extremes (Raleigh for warm temperate, Tasmania for cold oceanic and Queensland for hot tropical). The Raleigh population showed the highest mortality to DDT, whereas the Queensland population, epicentre for derived alleles of the resistance gene Cyp6g1, showed the lowest. Interaction between insecticide and temperature strongly affected mortality, particularly for the Tasmanian population. Activity profiles analysed using self-organizing maps show that the insecticide promoted an early response, whereas elevated temperature promoted a later response. These distinctive early or later activity phases revealed similar responses to temperature and DDT dose alone but with more or less genetic variance depending on the population. This change in genetic variance among populations suggests that selection particularly depleted genetic variance for DDT response in the Queensland population. Finally, despite similar (co)variation between traits in benign conditions, the genetic responses across population differed under stressful conditions. This showed how stress-responsive genetic variation only reveals itself in specific conditions and thereby escapes potential trade-offs in benign environments. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Rare Copy Number Deletions Predict Individual Variation in Intelligence

PubMed Central

Yeo, Ronald A.; Gangestad, Steven W.; Liu, Jingyu; Calhoun, Vince D.; Hutchison, Kent E.

2011-01-01

Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in “mutation load” emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent) copy number variations (CNVs), and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01). As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES), we also examined the impact of ethnicity (Anglo/White vs. Other), as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less) adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed. PMID:21298096

Maintenance of genetic diversity through plant-herbivore interactions

PubMed Central

Gloss, Andrew D.; Dittrich, Anna C. Nelson; Goldman-Huertas, Benjamin; Whiteman, Noah K.

2013-01-01

Identifying the factors governing the maintenance of genetic variation is a central challenge in evolutionary biology. New genomic data, methods and conceptual advances provide increasing evidence that balancing selection, mediated by antagonistic species interactions, maintains functionally-important genetic variation within species and natural populations. Because diverse interactions between plants and herbivorous insects dominate terrestrial communities, they provide excellent systems to address this hypothesis. Population genomic studies of Arabidopsis thaliana and its relatives suggest spatial variation in herbivory maintains adaptive genetic variation controlling defense phenotypes, both within and among populations. Conversely, inter-species variation in plant defenses promotes adaptive genetic variation in herbivores. Emerging genomic model herbivores of Arabidopsis could illuminate how genetic variation in herbivores and plants interact simultaneously. PMID:23834766

Maintenance of genetic variation in human personality: Testing evolutionary models by estimating heritability due to common causal variants and investigating the effect of distant inbreeding

PubMed Central

Verweij, Karin J.H.; Yang, Jian; Lahti, Jari; Veijola, Juha; Hintsanen, Mirka; Pulkki-Råback, Laura; Heinonen, Kati; Pouta, Anneli; Pesonen, Anu-Katriina; Widen, Elisabeth; Taanila, Anja; Isohanni, Matti; Miettunen, Jouko; Palotie, Aarno; Penke, Lars; Service, Susan K.; Heath, Andrew C.; Montgomery, Grant W.; Raitakari, Olli; Kähönen, Mika; Viikari, Jorma; Räikkönen, Katri; Eriksson, Johan G; Keltikangas-Järvinen, Liisa; Lehtimäki, Terho; Martin, Nicholas G.; Järvelin, Marjo-Riitta; Visscher, Peter M.; Keller, Matthew C.; Zietsch, Brendan P.

2012-01-01

Personality traits are basic dimensions of behavioural variation, and twin, family, and adoption studies show that around 30% of the between-individual variation is due to genetic variation. There is rapidly-growing interest in understanding the evolutionary basis of this genetic variation. Several evolutionary mechanisms could explain how genetic variation is maintained in traits, and each of these makes predictions in terms of the relative contribution of rare and common genetic variants to personality variation, the magnitude of nonadditive genetic influences, and whether personality is affected by inbreeding. Using genome-wide SNP data from >8,000 individuals, we estimated that little variation in the Cloninger personality dimensions (7.2% on average) is due to the combined effect of common, additive genetic variants across the genome, suggesting that most heritable variation in personality is due to rare variant effects and/or a combination of dominance and epistasis. Furthermore, higher levels of inbreeding were associated with less socially-desirable personality trait levels in three of the four personality dimensions. These findings are consistent with genetic variation in personality traits having been maintained by mutation-selection balance. PMID:23025612

Multiple Quantitative Trait Loci Influence the Shape of a Male-Specific Genital Structure in Drosophila melanogaster

PubMed Central

McNeil, Casey L.; Bain, Clint L.; Macdonald, Stuart J.

2011-01-01

The observation that male genitalia diverge more rapidly than other morphological traits during evolution is taxonomically widespread and likely due to some form of sexual selection. One way to elucidate the evolutionary forces acting on these traits is to detail the genetic architecture of variation both within and between species, a program of research that is considerably more tractable in a model system. Drosophila melanogaster and its sibling species, D. simulans, D. mauritiana, and D. sechellia, are morphologically distinguishable only by the shape of the posterior lobe, a male-specific elaboration of the genital arch. We extend earlier studies identifying quantitative trait loci (QTL) responsible for lobe divergence across species and report the first genetic dissection of lobe shape variation within a species. Using an advanced intercross mapping design, we identify three autosomal QTL contributing to the difference in lobe shape between a pair of D. melanogaster inbred lines. The QTL each contribute 4.6–10.7% to shape variation, and two show a significant epistatic interaction. Interestingly, these intraspecific QTL map to the same locations as interspecific lobe QTL, implying some shared genetic control of the trait within and between species. As a first step toward a mechanistic understanding of natural lobe shape variation, we find an association between our QTL data and a set of genes that show sex-biased expression in the developing genital imaginal disc (the precursor of the adult genitalia). These genes are good candidates to harbor naturally segregating polymorphisms contributing to posterior lobe shape. PMID:22384345

The emergence of human-evolutionary medical genomics

PubMed Central

Crespi, Bernard J

2011-01-01

In this review, I describe how evolutionary genomics is uniquely suited to spearhead advances in understanding human disease risk, owing to the privileged position of genes as fundamental causes of phenotypic variation, and the ability of population genetic and phylogenetic methods to robustly infer processes of natural selection, drift, and mutation from genetic variation at the levels of family, population, species, and clade. I first provide an overview of models for the origins and maintenance of genetically based disease risk in humans. I then discuss how analyses of genetic disease risk can be dovetailed with studies of positive and balancing selection, to evaluate the degree to which the ‘genes that make us human’ also represent the genes that mediate risk of polygenic disease. Finally, I present four basic principles for the nascent field of human evolutionary medical genomics, each of which represents a process that is nonintuitive from a proximate perspective. Joint consideration of these principles compels novel forms of interdisciplinary analyses, most notably studies that (i) analyze tradeoffs at the level of molecular genetics, and (ii) identify genetic variants that are derived in the human lineage or in specific populations, and then compare individuals with derived versus ancestral alleles. PMID:25567974

The Effect of an Extreme and Prolonged Population Bottleneck on Patterns of Deleterious Variation: Insights from the Greenlandic Inuit.

PubMed

Pedersen, Casper-Emil T; Lohmueller, Kirk E; Grarup, Niels; Bjerregaard, Peter; Hansen, Torben; Siegismund, Hans R; Moltke, Ida; Albrechtsen, Anders

2017-02-01

The genetic consequences of population bottlenecks on patterns of deleterious genetic variation in human populations are of tremendous interest. Based on exome sequencing of 18 Greenlandic Inuit we show that the Inuit have undergone a severe ∼20,000-year-long bottleneck. This has led to a markedly more extreme distribution of allele frequencies than seen for any other human population tested to date, making the Inuit the perfect population for investigating the effect of a bottleneck on patterns of deleterious variation. When comparing proxies for genetic load that assume an additive effect of deleterious alleles, the Inuit show, at most, a slight increase in load compared to European, East Asian, and African populations. Specifically, we observe <4% increase in the number of derived deleterious alleles in the Inuit. In contrast, proxies for genetic load under a recessive model suggest that the Inuit have a significantly higher load (20% increase or more) compared to other less bottlenecked human populations. Forward simulations under realistic models of demography support our empirical findings, showing up to a 6% increase in the genetic load for the Inuit population across all models of dominance. Further, the Inuit population carries fewer deleterious variants than other human populations, but those that are present tend to be at higher frequency than in other populations. Overall, our results show how recent demographic history has affected patterns of deleterious variants in human populations. Copyright © 2017 by the Genetics Society of America.

Geographic pattern of genetic variation in the European globeflower Trollius europaeus L. (Ranunculaceae) inferred from amplified fragment length polymorphism markers.

PubMed

Despres, Laurence; Loriot, Sandrine; Gaudeul, Myriam

2002-11-01

The distribution of genetic variation and the phylogenetic relationships between 18 populations of the arctic-alpine plant Trollius europaeus were analysed in three main regions (Alps, Pyrenees and Fennoscandia) by using dominant AFLP markers. Analysis of molecular variance revealed that most of the genetic variability was found within populations (64%), although variation among regions (17%) and among populations within regions (19%) was highly significant (P < 0.001). Accordingly, the global fixation index FST averaged over loci was high (0.39). The among-population differentiation indicates restricted gene flow, congruent with limited dispersal of specific globeflower's pollinating flies (Chiastocheta spp.). Within-population diversity levels were significantly higher in the Alps (mean Nei's expected heterozygosity HE = 0.229) than in the Pyrenees (HE= 0.197) or in Fennoscandia (HE = 0.158). This finding is congruent with the species-richness of the associated flies, which is maximum in the Alps. We discuss the processes involved in shaping observed patterns of genetic diversity within and among T. europaeus populations. Genetic drift is the major factor acting on the small Pyrenean populations at the southern edge of T. europaeus distribution, while large Fennoscandian populations result probably from a founder effect followed by demographic expansion. The Alpine populations represent moderately fragmented relics of large southern ancestral populations. The patterns of genetic variability observed in the host plant support the hypothesis of sympatric speciation in associated flies, rather than recurrent allopatric speciations.

Temporal differentiation across a West-European Y-chromosomal cline: genealogy as a tool in human population genetics.

PubMed

Larmuseau, Maarten H D; Ottoni, Claudio; Raeymaekers, Joost A M; Vanderheyden, Nancy; Larmuseau, Hendrik F M; Decorte, Ronny

2012-04-01

The pattern of population genetic variation and allele frequencies within a species are unstable and are changing over time according to different evolutionary factors. For humans, it is possible to combine detailed patrilineal genealogical records with deep Y-chromosome (Y-chr) genotyping to disentangle signals of historical population genetic structures because of the exponential increase in genetic genealogical data. To test this approach, we studied the temporal pattern of the 'autochthonous' micro-geographical genetic structure in the region of Brabant in Belgium and the Netherlands (Northwest Europe). Genealogical data of 881 individuals from Northwest Europe were collected, from which 634 family trees showed a residence within Brabant for at least one generation. The Y-chr genetic variation of the 634 participants was investigated using 110 Y-SNPs and 38 Y-STRs and linked to particular locations within Brabant on specific time periods based on genealogical records. Significant temporal variation in the Y-chr distribution was detected through a north-south gradient in the frequencies distribution of sub-haplogroup R1b1b2a1 (R-U106), next to an opposite trend for R1b1b2a2g (R-U152). The gradient on R-U106 faded in time and even became totally invisible during the Industrial Revolution in the first half of the nineteenth century. Therefore, genealogical data for at least 200 years are required to study small-scale 'autochthonous' population structure in Western Europe.

Epstein-Barr virus strains and variations: Geographic or disease-specific variants?

PubMed

Neves, Marco; Marinho-Dias, Joana; Ribeiro, Joana; Sousa, Hugo

2017-03-01

The Epstein-Barr Virus (EBV) is associated with the development of several diseases, including infectious mononucleosis (IM), Burkitt's Lymphoma (BL), Nasopharyngeal Carcinoma, and other neoplasias. The publication of EBV genome 1984 led to several studies regarding the identification of different viral strains. Currently, EBV is divided into EBV type 1 (B95-8 strain) and EBV type 2 (AG876 strain), also known as type A and type B, which have been distinguished based upon genetic differences in the Epstein-Barr nuclear antigens (EBNAs) sequence. Several other EBV strains have been described in the past 10 years considering variations on EBV genome, and many have attempted to clarify if these variations are ethnic or geographically correlated, or if they are disease related. Indeed, there is an increasing interest to describe possible specific disease associations, with emphasis on different malignancies. These studies aim to clarify if these variations are ethnic or geographically correlated, or if they are disease related, thus being important to characterize the epidemiologic genetic distribution of EBV strains on our population. Here, we review the current knowledge on the different EBV strains and variants and its association with different diseases. J. Med. Virol. 89:373-387, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Alcohol-related Genes Show an Enrichment of Associations with a Persistent Externalizing Factor

PubMed Central

Ashenhurst, James R.; Harden, K. Paige; Corbin, William R.; Fromme, Kim

2016-01-01

Research using twins has found that much of the variability in externalizing phenotypes – including alcohol and drug use, impulsive personality traits, risky sex and property crime – is explained by genetic factors. Nevertheless, identification of specific genes and variants associated with these traits has proven to be difficult, likely because individual differences in externalizing are explained by many genes of small individual effect. Moreover, twin research indicates that heritable variance in externalizing behaviors is mostly shared across the externalizing spectrum rather than specific to any behavior. We use a longitudinal, “deep phenotyping” approach to model a general externalizing factor reflecting persistent engagement in a variety of socially problematic behaviors measured at eleven assessment occasions spanning early adulthood (ages 18 to 28). In an ancestrally homogenous sample of non-Hispanic Whites (N = 337), we then tested for enrichment of associations between the persistent externalizing factor and a set of 3,281 polymorphisms within 104 genes that were previously identified as associated with alcohol-use behaviors. Next we tested for enrichment among domain-specific factors (e.g., property crime) composed of residual variance not accounted for by the common factor. Significance was determined relative to bootstrapped empirical thresholds derived from permutations of phenotypic data. Results indicated significant enrichment of genetic associations for persistent externalizing, but not for domain-specific factors. Consistent with twin research findings, these results suggest that genetic variants are broadly associated with externalizing behaviors rather than unique to specific behaviors. General Scientific Summary This study shows that variation in 104 genes is associated with socially problematic “externalizing” behavior, including substance misuse, property crime, risky sex, and aspects of impulsive personality. Importantly, this association was with the common variation across these behaviors rather than with the variation unique to any given behavior. The manuscript demonstrates a potentially advantageous technique for relating sets of hypothesized genes to complex traits or behaviors. PMID:27505405

Genetic variation and relationships of four species of medically important echinostomes (Trematoda: Echinostomatidae) in South-East Asia.

PubMed

Saijuntha, Weerachai; Sithithaworn, Paiboon; Duenngai, Kunyarat; Kiatsopit, Nadda; Andrews, Ross H; Petney, Trevor N

2011-03-01

Multilocus enzyme electrophoresis (MEE) and DNA sequencing of the mitochondrial cytochrome c oxidase subunit 1 (CO1) gene were used to genetically compare four species of echinostomes of human health importance. Fixed genetic differences among adults of Echinostoma revolutum, Echinostoma malayanum, Echinoparyphium recurvatum and Hypoderaeum conoideum were detected at 51-75% of the enzyme loci examined, while interspecific differences in CO1 sequence were detected at 16-32 (8-16%) of the 205 alignment positions. The results of the MEE analyses also revealed fixed genetic differences between E. revolutum from Thailand and Lao PDR at five (19%) of 27 loci, which could either represent genetic variation between geographically separated populations of a single species, or the existence of a cryptic (i.e. genetically distinct but morphologically similar) species. However, there was no support for the existence of cryptic species within E. revolutum based on the CO1 sequence between the two geographical areas sampled. Genetic variation in CO1 sequence was also detected among E. malayanum from three different species of snail intermediate host. Separate phylogenetic analyses of the MEE and DNA sequence data revealed that the two species of Echinostoma (E. revolutum and E. malayanum) did not form a monophyletic clade. These results, together with the large number of morphologically similar species with inadequate descriptions, poor specific diagnoses and extensive synonymy, suggest that the morphological characters used for species taxonomy of echinostomes in South-East Asia should be reconsidered according to the concordance of biology, morphology and molecular classification. Copyright © 2010 Elsevier B.V. All rights reserved.

The role of latitudinal, genetic and temperature variation in the induction of diapause of Papilio glaucus (Lepidoptera: Papilionidae).

PubMed

Ryan, Sean F; Valella, Patti; Thivierge, Gabrielle; Aardema, Matthew L; Scriber, J Mark

2018-04-01

A key adaptation in insects for dealing with variable environmental conditions is the ability to diapause. The tiger swallowtail butterflies, Papilio glaucus and P. canadensis are ideal species to explore the genetic causes and population genetic consequences of diapause because divergence in this trait is believed to be a salient factor in maintaining a hybrid zone between these species. Yet little is known about the factors that influence diapause induction in this system. Here we explored how spatial (latitudinal), environmental (temperature) and genetic (hybridization) factors affect diapause induction in this system. Specifically, a series of growth chamber experiments using wild caught individuals from across the eastern United States were performed to: (1) evaluate how critical photoperiod varies with latitude, (2) isolate the stage in which induction occurs, (3) test whether changes in temperature affected rates of diapause induction, and (4) explore how the incidence of diapause is affected in hybrid offspring. We find that induction occurs in the larval stage, is not sensitive to a relatively broad range of temperatures, appears to have a complex genetic basis (i.e., is not simply a dominant trait following a Mendelian inheritance pattern) and that the critical photoperiod increases by 0.4 h with each increasing degree in latitude. This work deepens our understanding of how spatial, environmental and genetic variation influences a key seasonal adaptation (diapause induction) in a well-developed ecological model system and will make possible future studies that explore how climatic variation affects the population dynamics and genetics of this system. © 2016 Institute of Zoology, Chinese Academy of Sciences.

Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges.

PubMed

Piasecka, Barbara; Duffy, Darragh; Urrutia, Alejandra; Quach, Hélène; Patin, Etienne; Posseme, Céline; Bergstedt, Jacob; Charbit, Bruno; Rouilly, Vincent; MacPherson, Cameron R; Hasan, Milena; Albaud, Benoit; Gentien, David; Fellay, Jacques; Albert, Matthew L; Quintana-Murci, Lluis

2018-01-16

The contribution of host genetic and nongenetic factors to immunological differences in humans remains largely undefined. Here, we generated bacterial-, fungal-, and viral-induced immune transcriptional profiles in an age- and sex-balanced cohort of 1,000 healthy individuals and searched for the determinants of immune response variation. We found that age and sex affected the transcriptional response of most immune-related genes, with age effects being more stimulus-specific relative to sex effects, which were largely shared across conditions. Although specific cell populations mediated the effects of age and sex on gene expression, including CD8 + T cells for age and CD4 + T cells and monocytes for sex, we detected a direct effect of these intrinsic factors for the majority of immune genes. The mapping of expression quantitative trait loci (eQTLs) revealed that genetic factors had a stronger effect on immune gene regulation than age and sex, yet they affected a smaller number of genes. Importantly, we identified numerous genetic variants that manifested their regulatory effects exclusively on immune stimulation, including a Candida albicans -specific master regulator at the CR1 locus. These response eQTLs were enriched in disease-associated variants, particularly for autoimmune and inflammatory disorders, indicating that differences in disease risk may result from regulatory variants exerting their effects only in the presence of immune stress. Together, this study quantifies the respective effects of age, sex, genetics, and cellular heterogeneity on the interindividual variability of immune responses and constitutes a valuable resource for further exploration in the context of different infection risks or disease outcomes. Copyright © 2018 the Author(s). Published by PNAS.

Whole-Genome Analysis of Three Yeast Strains Used for Production of Sherry-Like Wines Revealed Genetic Traits Specific to Flor Yeasts

PubMed Central

Eldarov, Mikhail A.; Beletsky, Alexey V.; Tanashchuk, Tatiana N.; Kishkovskaya, Svetlana A.; Ravin, Nikolai V.; Mardanov, Andrey V.

2018-01-01

Flor yeast strains represent a specialized group of Saccharomyces cerevisiae yeasts used for biological wine aging. We have sequenced the genomes of three flor strains originated from different geographic regions and used for production of sherry-like wines in Russia. According to the obtained phylogeny of 118 yeast strains, flor strains form very tight cluster adjacent to the main wine clade. SNP analysis versus available genomes of wine and flor strains revealed 2,270 genetic variants in 1,337 loci specific to flor strains. Gene ontology analysis in combination with gene content evaluation revealed a complex landscape of possibly adaptive genetic changes in flor yeast, related to genes associated with cell morphology, mitotic cell cycle, ion homeostasis, DNA repair, carbohydrate metabolism, lipid metabolism, and cell wall biogenesis. Pangenomic analysis discovered the presence of several well-known “non-reference” loci of potential industrial importance. Events of gene loss included deletions of asparaginase genes, maltose utilization locus, and FRE-FIT locus involved in iron transport. The latter in combination with a flor-yeast-specific mutation in the Aft1 transcription factor gene is likely to be responsible for the discovered phenotype of increased iron sensitivity and improved iron uptake of analyzed strains. Expansion of the coding region of the FLO11 flocullin gene and alteration of the balance between members of the FLO gene family are likely to positively affect the well-known propensity of flor strains for velum formation. Our study provides new insights in the nature of genetic variation in flor yeast strains and demonstrates that different adaptive properties of flor yeast strains could have evolved through different mechanisms of genetic variation. PMID:29867869

Biological variation in musculoskeletal injuries: current knowledge, future research and practical implications.

PubMed

Collins, Malcolm; September, Alison V; Posthumus, Michael

2015-12-01

Evidence from familial and genetic association studies have reported that DNA sequence variants play an important role, together with non-genetic factors, in the aetiology of both exercise-associated and occupational-associated acute and chronic musculoskeletal soft tissue injuries. The associated variants, which have been identified to date, may contribute to the interindividual variation in the structure and, by implication, mechanical properties of the collagen fibril and surrounding matrix within musculoskeletal soft tissues, as well as their response to mechanical loading and other stimuli. Future work should focus on the establishment of multidisciplinary international consortia for the identification of biologically relevant variants involved in modulating injury risk. These consortia will improve the limitations of the published hypothesis-driven genetic association studies, since they will allow resources to be pooled in recruiting large well-characterised cohorts required for whole-genome screening. Finally, clinicians and coaches need to be aware that many direct-to-consumer companies are currently marketing genetic tests directly to athletes without it being requested by an appropriately qualified healthcare professional, and without interpretation alongside other clinical indicators or lifestyle factors. These specific genetic tests are premature and are not necessarily required to evaluate susceptibility to musculoskeletal soft tissue injury. Current practice should rather consider susceptibility through known risk factors such as a positive family history of a specific injury, a history of other tendon and/or ligament injuries and participation in activities associated with the specific musculoskeletal injuries. Potential susceptible athletes may then be individually managed to reduce their risk profile. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Culture modifies expectations of kinship and sex-biased dispersal patterns: a case study of patrilineality and patrilocality in tribal Yemen.

PubMed

Raaum, Ryan L; Al-Meeri, Ali; Mulligan, Connie J

2013-04-01

Studies of the impact of post-marital residence patterns on the distribution of genetic variation within populations have returned conflicting results. These studies have generally examined genetic diversity within and between groups with different post-marriage residence patterns. Here, we directly examine Y chromosome microsatellite variation in individuals carrying a chromosome in the same Y haplogroup. We analyze Y chromosome data from two samples of Yemeni males: a sample representing the entire country and a sample from a large highland village. Our results support a normative patrilocality in highland Yemeni tribal populations, but also suggest that patrilocality is violated often enough to break down the expected correlation of genetic and geographic distance. We propose that a great deal of variation in male dispersal distance distributions is subsumed under the "patrilocal" label and that few human societies are likely to realize the idealized male dispersal distribution expected under strict patrilocality. In addition, we found almost no specific correspondence between social kinship and genetic patriline at the level of the clan (large, extended patrilineal kinship group) within a large, highland Yemeni village. We discuss ethnographic accounts that offer several cultural practices that explain exceptions to patrilocality and means by which social kinship and genetic patriline may become disentangled. Copyright © 2013 Wiley Periodicals, Inc.

Integrating common and rare genetic variation in diverse human populations.

PubMed

Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

2010-09-02

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of

Genetic and Environmental Factors Associated with Cannabis Involvement

PubMed Central

Bogdan, Ryan; Winstone, Jonathan MA; Agrawal, Arpana

2016-01-01

Approximately 50-70% of the variation in cannabis use and use disorders can be attributed to heritable factors. For cannabis use, the remaining variance can be parsed in to familial and person-specific environmental factors while for use disorders, only the latter contribute. While numerous candidate gene studies have identified the role of common variation influencing liability to cannabis involvement, replication has been elusive. To date, no genomewide association study has been sufficiently powered to identify significant loci. Despite this, studies adopting polygenic techniques and integrating genetic variation with neural phenotypes and measures of environmental risk, such as childhood adversity, are providing promising new leads. It is likely that the small effect sizes associated with variants related to cannabis involvement will only be robustly identified in substantially larger samples. Results of such large-scale efforts will provide valuable single variant targets for translational research in neurogenetic, pharmacogenetic and non-human animal models as well as polygenic risk indices that can be used to explore a host of other genetic hypotheses related to cannabis use and misuse. PMID:27642547

Genomic determinants of epidermal appendage patterning and structure in domestic birds.

PubMed

Boer, Elena F; Van Hollebeke, Hannah F; Shapiro, Michael D

2017-09-15

Variation in regional identity, patterning, and structure of epidermal appendages contributes to skin diversity among many vertebrate groups, and is perhaps most striking in birds. In pioneering work on epidermal appendage patterning, John Saunders and his contemporaries took advantage of epidermal appendage diversity within and among domestic chicken breeds to establish the importance of mesoderm-ectoderm signaling in determining skin patterning. Diversity in chickens and other domestic birds, including pigeons, is driving a new wave of research to dissect the molecular genetic basis of epidermal appendage patterning. Domestic birds are not only outstanding models for embryonic manipulations, as Saunders recognized, but they are also ideal genetic models for discovering the specific genes that control normal development and the mutations that contribute to skin diversity. Here, we review recent genetic and genomic approaches to uncover the basis of epidermal macropatterning, micropatterning, and structural variation. We also present new results that confirm expression changes in two limb identity genes in feather-footed pigeons, a case of variation in appendage structure and identity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Rate of evolutionary change in cranial morphology of the marsupial genus Monodelphis is constrained by the availability of additive genetic variation

PubMed Central

Porto, Arthur; Sebastião, Harley; Pavan, Silvia Eliza; VandeBerg, John L.; Marroig, Gabriel; Cheverud, James M.

2015-01-01

We tested the hypothesis that the rate of marsupial cranial evolution is dependent on the distribution of genetic variation in multivariate space. To do so, we carried out a genetic analysis of cranial morphological variation in laboratory strains of Monodelphis domestica and used estimates of genetic covariation to analyze the morphological diversification of the Monodelphis brevicaudata species group. We found that within-species genetic variation is concentrated in only a few axes of the morphospace and that this strong genetic covariation influenced the rate of morphological diversification of the brevicaudata group, with between-species divergence occurring fastest when occurring along the genetic line of least resistance. Accounting for the geometric distribution of genetic variation also increased our ability to detect the selective regimen underlying species diversification, with several instances of selection only being detected when genetic covariances were taken into account. Therefore, this work directly links patterns of genetic covariation among traits to macroevolutionary patterns of morphological divergence. Our findings also suggest that the limited distribution of Monodelphis species in morphospace is the result of a complex interplay between the limited dimensionality of available genetic variation and strong stabilizing selection along two major axes of genetic variation. PMID:25818173

The Effect of Common Inversion Polymorphisms In(2L)t and In(3R)Mo on Patterns of Transcriptional Variation in Drosophila melanogaster.

PubMed

Lavington, Erik; Kern, Andrew D

2017-11-06

Chromosomal inversions are a ubiquitous feature of genetic variation. Theoretical models describe several mechanisms by which inversions can drive adaptation and be maintained as polymorphisms. While inversions have been shown previously to be under selection, or contain genetic variation under selection, the specific phenotypic consequences of inversions leading to their maintenance remain unclear. Here we use genomic sequence and expression data from the Drosophila Genetic Reference Panel (DGRP) to explore the effects of two cosmopolitan inversions, In ( 2L ) t and In ( 3R ) Mo , on patterns of transcriptional variation. We demonstrate that each inversion has a significant effect on transcript abundance for hundreds of genes across the genome. Inversion-affected loci (IAL) appear both within inversions as well as on unlinked chromosomes. Importantly, IAL do not appear to be influenced by the previously reported genome-wide expression correlation structure. We found that five genes involved with sterol uptake, four of which are Niemann-Pick Type 2 orthologs, are upregulated in flies with In ( 3R ) Mo but do not have SNPs in linkage disequilibrium (LD) with the inversion. We speculate that this upregulation is driven by genetic variation in mod ( mdg4 ) that is in LD with In ( 3R ) Mo We find that there is little evidence for a regional or position effect of inversions on gene expression at the chromosomal level, but do find evidence for the distal breakpoint of In ( 3R ) Mo interrupting one gene and possibly disassociating the two flanking genes from regulatory elements. Copyright © 2017 Lavington and Kern.

The Effect of Common Inversion Polymorphisms In(2L)t and In(3R)Mo on Patterns of Transcriptional Variation in Drosophila melanogaster

PubMed Central

Lavington, Erik; Kern, Andrew D.

2017-01-01

Chromosomal inversions are a ubiquitous feature of genetic variation. Theoretical models describe several mechanisms by which inversions can drive adaptation and be maintained as polymorphisms. While inversions have been shown previously to be under selection, or contain genetic variation under selection, the specific phenotypic consequences of inversions leading to their maintenance remain unclear. Here we use genomic sequence and expression data from the Drosophila Genetic Reference Panel (DGRP) to explore the effects of two cosmopolitan inversions, In(2L)t and In(3R)Mo, on patterns of transcriptional variation. We demonstrate that each inversion has a significant effect on transcript abundance for hundreds of genes across the genome. Inversion-affected loci (IAL) appear both within inversions as well as on unlinked chromosomes. Importantly, IAL do not appear to be influenced by the previously reported genome-wide expression correlation structure. We found that five genes involved with sterol uptake, four of which are Niemann-Pick Type 2 orthologs, are upregulated in flies with In(3R)Mo but do not have SNPs in linkage disequilibrium (LD) with the inversion. We speculate that this upregulation is driven by genetic variation in mod(mdg4) that is in LD with In(3R)Mo. We find that there is little evidence for a regional or position effect of inversions on gene expression at the chromosomal level, but do find evidence for the distal breakpoint of In(3R)Mo interrupting one gene and possibly disassociating the two flanking genes from regulatory elements. PMID:28916647

Genetic differentiation of the mitochondrial cytochrome oxidase C subunit I gene in genus Paramecium (Protista, Ciliophora).

PubMed

Zhao, Yan; Gentekaki, Eleni; Yi, Zhenzhen; Lin, Xiaofeng

2013-01-01

The mitochondrial cytochrome c oxidase subunit I (COI) gene is being used increasingly for evaluating inter- and intra-specific genetic diversity of ciliated protists. However, very few studies focus on assessing genetic divergence of the COI gene within individuals and how its presence might affect species identification and population structure analyses. We evaluated the genetic variation of the COI gene in five Paramecium species for a total of 147 clones derived from 21 individuals and 7 populations. We identified a total of 90 haplotypes with several individuals carrying more than one haplotype. Parsimony network and phylogenetic tree analyses revealed that intra-individual diversity had no effect in species identification and only a minor effect on population structure. Our results suggest that the COI gene is a suitable marker for resolving inter- and intra-specific relationships of Paramecium spp.

Genetic Differentiation of the Mitochondrial Cytochrome Oxidase c Subunit I Gene in Genus Paramecium (Protista, Ciliophora)

PubMed Central

Zhao, Yan; Gentekaki, Eleni; Yi, Zhenzhen; Lin, Xiaofeng

2013-01-01

Background The mitochondrial cytochrome c oxidase subunit I (COI) gene is being used increasingly for evaluating inter- and intra-specific genetic diversity of ciliated protists. However, very few studies focus on assessing genetic divergence of the COI gene within individuals and how its presence might affect species identification and population structure analyses. Methodology/Principal findings We evaluated the genetic variation of the COI gene in five Paramecium species for a total of 147 clones derived from 21 individuals and 7 populations. We identified a total of 90 haplotypes with several individuals carrying more than one haplotype. Parsimony network and phylogenetic tree analyses revealed that intra-individual diversity had no effect in species identification and only a minor effect on population structure. Conclusions Our results suggest that the COI gene is a suitable marker for resolving inter- and intra-specific relationships of Paramecium spp. PMID:24204730

Variation in MHC genotypes in two populations of house sparrow (Passer domesticus) with different population histories.

PubMed

Borg, Asa Alexandra; Pedersen, Sindre Andre; Jensen, Henrik; Westerdahl, Helena

2011-10-01

Small populations are likely to have a low genetic ability for disease resistance due to loss of genetic variation through inbreeding and genetic drift. In vertebrates, the highest genetic diversity of the immune system is located at genes within the major histocompatibility complex (MHC). Interestingly, parasite-mediated selection is thought to potentially maintain variation at MHC loci even in populations that are monomorphic at other loci. Therefore, general loss of genetic variation in the genome may not necessarily be associated with low variation at MHC loci. We evaluated inter- and intrapopulation variation in MHC genotypes between an inbred (Aldra) and a relatively outbred population (Hestmannøy) of house sparrows (Passer domesticus) in a metapopulation at Helgeland, Norway. Genomic (gDNA) and transcribed (cDNA) alleles of functional MHC class I and IIB loci, along with neutral noncoding microsatellite markers, were analyzed to obtain relevant estimates of genetic variation. We found lower allelic richness in microsatellites in the inbred population, but high genetic variation in MHC class I and IIB loci in both populations. This suggests that also the inbred population could be under balancing selection to maintain genetic variation for pathogen resistance.

Variation in MHC genotypes in two populations of house sparrow (Passer domesticus) with different population histories

PubMed Central

Borg, Åsa Alexandra; Pedersen, Sindre Andre; Jensen, Henrik; Westerdahl, Helena

2011-01-01

Small populations are likely to have a low genetic ability for disease resistance due to loss of genetic variation through inbreeding and genetic drift. In vertebrates, the highest genetic diversity of the immune system is located at genes within the major histocompatibility complex (MHC). Interestingly, parasite-mediated selection is thought to potentially maintain variation at MHC loci even in populations that are monomorphic at other loci. Therefore, general loss of genetic variation in the genome may not necessarily be associated with low variation at MHC loci. We evaluated inter- and intrapopulation variation in MHC genotypes between an inbred (Aldra) and a relatively outbred population (Hestmannøy) of house sparrows (Passer domesticus) in a metapopulation at Helgeland, Norway. Genomic (gDNA) and transcribed (cDNA) alleles of functional MHC class I and IIB loci, along with neutral noncoding microsatellite markers, were analyzed to obtain relevant estimates of genetic variation. We found lower allelic richness in microsatellites in the inbred population, but high genetic variation in MHC class I and IIB loci in both populations. This suggests that also the inbred population could be under balancing selection to maintain genetic variation for pathogen resistance. PMID:22393491

New genes linked to lung cancer susceptibility in Asian women

Cancer.gov

An international group of scientists has identified three genes that predispose Asian women who have never smoked to lung cancer. The discovery of specific genetic variations, which have not previously been associated with lung cancer risk in other popul

Avian Disease & Oncology Lab (ADOL) Research Update

USDA-ARS?s Scientific Manuscript database

Employing Genomics, Epigenetics, and Immunogenetics to Control Diseases Induced by Avian Tumor Viruses - Gene expression is a major factor accounting for phenotypic variation. Taking advantage of allele-specific expression (ASE) screens, we found the use of genetic markers was superior to traditiona...

Wild worm embryogenesis harbors ubiquitous polygenic modifier variation

PubMed Central

Paaby, Annalise B; White, Amelia G; Riccardi, David D; Gunsalus, Kristin C; Piano, Fabio; Rockman, Matthew V

2015-01-01

Embryogenesis is an essential and stereotypic process that nevertheless evolves among species. Its essentiality may favor the accumulation of cryptic genetic variation (CGV) that has no effect in the wild-type but that enhances or suppresses the effects of rare disruptions to gene function. Here, we adapted a classical modifier screen to interrogate the alleles segregating in natural populations of Caenorhabditis elegans: we induced gene knockdowns and used quantitative genetic methodology to examine how segregating variants modify the penetrance of embryonic lethality. Each perturbation revealed CGV, indicating that wild-type genomes harbor myriad genetic modifiers that may have little effect individually but which in aggregate can dramatically influence penetrance. Phenotypes were mediated by many modifiers, indicating high polygenicity, but the alleles tend to act very specifically, indicating low pleiotropy. Our findings demonstrate the extent of conditional functionality in complex trait architecture. DOI: http://dx.doi.org/10.7554/eLife.09178.001 PMID:26297805

Population dynamics of Aedes aegypti from a dengue hyperendemic urban setting in Colombia.

PubMed

Ocampo, Clara B; Wesson, Dawn M

2004-10-01

This study evaluated if the Aedes aegypti population in the city of Cali, Colombia was composed of genetically distinct local populations with different levels of insecticide resistance and dengue vector competence. Insecticide resistance was assayed biochemically and was associated with varying levels of mixed-function oxidases and non-specific esterases. The genes encoding those enzymes were under selective pressure from insecticides used to suppress Ae. aegypti populations. Vector competence showed heterogeneity among the vector populations ranging from 19% to 60%. Population genetic analysis of random amplified polymorphic DNA-polymerase chain reaction products, expressed as genetic distance, Wright's F(st), and migration rate (Nm), demonstrated moderate genetic differentiation among Ae. aegypti from four sites (F(st) = 0.085). The results from all characteristics evaluated in the study demonstrated spatial and temporal variation between Ae. aegypti populations. At any specific time, the local populations of Ae. aegypti were genetically differentiated and unique with respect to insecticide resistance and vector competence. Both characteristics changed independently.

Comparative analyses of genetic/epigenetic diversities and structures in a wild barley species (Hordeum brevisubulatum) using MSAP, SSAP and AFLP.

PubMed

Shan, X H; Li, Y D; Liu, X M; Wu, Y; Zhang, M Z; Guo, W L; Liu, B; Yuan, Y P

2012-08-17

We analyzed genetic diversity and population genetic structure of four artificial populations of wild barley (Hordeum brevisubulatum); 96 plants collected from the Songnen Prairie in northeastern China were analyzed using amplified fragment length polymorphism (AFLP), specific-sequence amplified polymorphism (SSAP) and methylation-sensitive amplified polymorphism (MSAP) markers. Indices of (epi-)genetic diversity, (epi-)genetic distance, gene flow, genotype frequency, cluster analysis, PCA analysis and AMOVA analysis generated from MSAP, AFLP and SSAP markers had the same trend. We found a high level of correlation in the artificial populations between MSAP, SSAP and AFLP markers by the Mantel test (r > 0.8). This is incongruent with previous findings showing that there is virtually no correlation between DNA methylation polymorphism and classical genetic variation; the high level of genetic polymorphism could be a result of epigenetic regulation. We compared our results with data from natural populations. The population diversity of the artificial populations was lower. However, different from what was found using AFLP and SSAP, based on MSAP results the methylation polymorphism of the artificial populations was not significantly reduced. This leads us to suggest that the DNA methylation pattern change in H. brevisubulatum populations is not only related to DNA sequence variation, but is also regulated by other controlling systems.

Genetic variability of milk fatty acids.

PubMed

Arnould, V M-R; Soyeurt, H

2009-01-01

The milk fatty acid (FA) profile is far from the optimal fat composition in regards to human health. The natural sources of variation, such as feeding or genetics, could be used to increase the concentrations of unsaturated fatty acids. The impact of feeding is well described. However, genetic effects on the milk FA composition begin to be extensively studied. This paper summarizes the available information about the genetic variability of FAs. The greatest breed differences in FA composition are observed between Holstein and Jersey milk. Milk fat of the latter breed contains higher concentrations of saturated FAs, especially short-chain FAs. The variation of the delta-9 desaturase activity estimated from specific FA ratios could explain partly these breed differences. The choice of a specific breed seems to be a possibility to improve the nutritional quality of milk fat. Generally, the proportions of FAs in milk are more heritable than the proportions of these same FAs in fat. Heritability estimates range from 0.00 to 0.54. The presence of some single nucleotide polymorphisms could explain partly the observed individual genetic variability. The polymorphisms detected on SCD1 and DGAT1 genes influence the milk FA composition. The SCD1 V allele increases the unsaturation of C16 and C18. The DGAT1 A allele is related to the unsaturation of C18. So, a combination of the molecular and quantitative approaches should be used to develop tools helping farmers in the selection of their animals to improve the nutritional quality of the produced milk fat.

Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity

PubMed Central

Bearoff, Frank; del Rio, Roxana; Case, Laure K.; Dragon, Julie A.; Nguyen-Vu, Trang; Lin, Chin-Yo; Blankenhorn, Elizabeth P.; Teuscher, Cory; Krementsov, Dimitry N.

2016-01-01

Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases, such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naïve immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific, and sex-specific. Bioinformatic analysis of the genetically-controlled transcript networks reveals reduced cell type-specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared to PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease. PMID:27653816

Somatic Genetic Variation in Solid Pseudopapillary Tumor of the Pancreas by Whole Exome Sequencing

PubMed Central

Guo, Meng; Luo, Guopei; Jin, Kaizhou; Long, Jiang; Cheng, He; Lu, Yu; Wang, Zhengshi; Yang, Chao; Xu, Jin; Ni, Quanxing; Yu, Xianjun; Liu, Chen

2017-01-01

Solid pseudopapillary tumor of the pancreas (SPT) is a rare pancreatic disease with a unique clinical manifestation. Although CTNNB1 gene mutations had been universally reported, genetic variation profiles of SPT are largely unidentified. We conducted whole exome sequencing in nine SPT patients to probe the SPT-specific insertions and deletions (indels) and single nucleotide polymorphisms (SNPs). In total, 54 SNPs and 41 indels of prominent variations were demonstrated through parallel exome sequencing. We detected that CTNNB1 mutations presented throughout all patients studied (100%), and a higher count of SNPs was particularly detected in patients with older age, larger tumor, and metastatic disease. By aggregating 95 detected variation events and viewing the interconnections among each of the genes with variations, CTNNB1 was identified as the core portion in the network, which might collaborate with other events such as variations of USP9X, EP400, HTT, MED12, and PKD1 to regulate tumorigenesis. Pathway analysis showed that the events involved in other cancers had the potential to influence the progression of the SNPs count. Our study revealed an insight into the variation of the gene encoding region underlying solid-pseudopapillary neoplasm tumorigenesis. The detection of these variations might partly reflect the potential molecular mechanism. PMID:28054945

Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice.

PubMed

Holland, Michelle L; Lowe, Robert; Caton, Paul W; Gemma, Carolina; Carbajosa, Guillermo; Danson, Amy F; Carpenter, Asha A M; Loche, Elena; Ozanne, Susan E; Rakyan, Vardhman K

2016-07-29

A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults. Copyright © 2016, American Association for the Advancement of Science.

Genetic Polymorphisms in Host Antiviral Genes: Associations with Humoral and Cellular Immunity to Measles Vaccine

PubMed Central

Haralambieva, Iana H.; Ovsyannikova, Inna G.; Umlauf, Benjamin J.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

2014-01-01

Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans. PMID:21939710

Footprints of ancient-balanced polymorphisms in genetic variation data from closely related species

PubMed Central

Gao, Ziyue; Przeworski, Molly; Sella, Guy

2015-01-01

When long-lasting, balancing selection can lead to “trans-species” polymorphisms that are shared by two or more species identical by descent. In such cases, the gene genealogy at the selected site clusters by allele instead of by species, and nearby neutral sites also have unusual genealogies because of linkage. While this scenario is expected to leave discernible footprints in genetic variation data, the specific patterns remain poorly characterized. Motivated by recent findings in primates, we focus on the case of a biallelic polymorphism under ancient balancing selection and derive approximations for summaries of the polymorphism data from two species. Specifically, we characterize the length of the segment that carries most of the footprints, the expected number of shared neutral single nucleotide polymorphisms (SNPs), and the patterns of allelic associations among them. We confirm the accuracy of our approximations by coalescent simulations. We further show that for humans and chimpanzees—more generally, for pairs of species with low genetic diversity levels—these patterns are highly unlikely to be generated by neutral recurrent mutations. We discuss the implications for the design and interpretation of genome scans for ancient balanced polymorphisms in primates and other taxa. PMID:25403856

On the importance of balancing selection in plants

PubMed Central

Delph, Lynda F.; Kelly, John K.

2013-01-01

Summary Balancing selection refers to a variety of selective regimes that maintain advantageous genetic diversity within populations. We review the history of the ideas regarding the types of selection that maintain such polymorphism in flowering plants, notably heterozygote advantage, negative frequency-dependent selection, and spatial heterogeneity. One shared feature of these mechanisms is that whether an allele is beneficial or detrimental is conditional on its frequency in the population. We highlight examples of balancing selection on a variety of discrete traits. These include the well-referenced case of self-incompatibility and recent evidence from species with nuclear-cytoplasmic gynodioecy, both of which exhibit trans-specific polymorphism, a hallmark of balancing selection. We also discuss and give examples of how spatial heterogeneity in particular, which is often thought unlikely to allow protected polymorphism, can maintain genetic variation in plants (which are rooted in place) as a result of microhabitat selection. Lastly, we discuss limitations of the protected polymorphism concept for quantitative traits, where selection can inflate the genetic variance without maintaining specific alleles indefinitely. We conclude that while discrete-morph variation provides the most unambiguous cases of protected polymorphism, they represent only a fraction of the balancing selection at work in plants. PMID:23952298

Glutamine Synthetase Is a Genetic Determinant of Cell Type–Specific Glutamine Independence in Breast Epithelia

PubMed Central

Kung, Hsiu-Ni; Marks, Jeffrey R.; Chi, Jen-Tsan

2011-01-01

Although significant variations in the metabolic profiles exist among different cells, little is understood in terms of genetic regulations of such cell type–specific metabolic phenotypes and nutrient requirements. While many cancer cells depend on exogenous glutamine for survival to justify the therapeutic targeting of glutamine metabolism, the mechanisms of glutamine dependence and likely response and resistance of such glutamine-targeting strategies among cancers are largely unknown. In this study, we have found a systematic variation in the glutamine dependence among breast tumor subtypes associated with mammary differentiation: basal- but not luminal-type breast cells are more glutamine-dependent and may be susceptible to glutamine-targeting therapeutics. Glutamine independence of luminal-type cells is associated mechanistically with lineage-specific expression of glutamine synthetase (GS). Luminal cells can also rescue basal cells in co-culture without glutamine, indicating a potential for glutamine symbiosis within breast ducts. The luminal-specific expression of GS is directly induced by GATA3 and represses glutaminase expression. Such distinct glutamine dependency and metabolic symbiosis is coupled with the acquisition of the GS and glutamine independence during the mammary differentiation program. Understanding the genetic circuitry governing distinct metabolic patterns is relevant to many symbiotic relationships among different cells and organisms. In addition, the ability of GS to predict patterns of glutamine metabolism and dependency among tumors is also crucial in the rational design and application of glutamine and other metabolic pathway targeted therapies. PMID:21852960

Genetic variation in the USDA Chamaecrista fasciculata collection

USDA-ARS?s Scientific Manuscript database

Germplasm collections serve as critical repositories of genetic variation. Characterizing genetic diversity in existing collections is necessary to maximize their utility and to guide future collecting efforts. We have used AFLP markers to characterize genetic variation in the USDA germplasm collect...

Evolution and inheritance of early embryonic patterning in D. simulans and D. sechellia

PubMed Central

Lott, Susan E.; Ludwig, Michael Z.; Kreitman, Martin

2010-01-01

Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation which selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth ‘stripe allometry’) in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species D. simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the “margin of error” for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness PMID:21121913

Multiple loci and genetic interactions involving flowering time genes regulate stem branching among natural variants of Arabidopsis.

PubMed

Huang, Xueqing; Ding, Jia; Effgen, Sigi; Turck, Franziska; Koornneef, Maarten

2013-08-01

Shoot branching is a major determinant of plant architecture. Genetic variants for reduced stem branching in the axils of cauline leaves of Arabidopsis were found in some natural accessions and also at low frequency in the progeny of multiparent crosses. Detailed genetic analysis using segregating populations derived from backcrosses with the parental lines and bulked segregant analysis was used to identify the allelic variation controlling reduced stem branching. Eight quantitative trait loci (QTLs) contributing to natural variation for reduced stem branching were identified (REDUCED STEM BRANCHING 1-8 (RSB1-8)). Genetic analysis showed that RSB6 and RSB7, corresponding to flowering time genes FLOWERING LOCUS C (FLC) and FRIGIDA (FRI), epistatically regulate stem branching. Furthermore, FLOWERING LOCUS T (FT), which corresponds to RSB8 as demonstrated by fine-mapping, transgenic complementation and expression analysis, caused pleiotropic effects not only on flowering time, but, in the specific background of active FRI and FLC alleles, also on the RSB trait. The consequence of allelic variation only expressed in late-flowering genotypes revealed novel and thus far unsuspected roles of several genes well characterized for their roles in flowering time control. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Assessment of imprinting- and genetic variation-dependent monoallelic expression using reciprocal allele descendants between human family trios.

PubMed

Chuang, Trees-Juen; Tseng, Yu-Hsiang; Chen, Chia-Ying; Wang, Yi-Da

2017-08-01

Genomic imprinting is an important epigenetic process that silences one of the parentally-inherited alleles of a gene and thereby exhibits allelic-specific expression (ASE). Detection of human imprinting events is hampered by the infeasibility of the reciprocal mating system in humans and the removal of ASE events arising from non-imprinting factors. Here, we describe a pipeline with the pattern of reciprocal allele descendants (RADs) through genotyping and transcriptome sequencing data across independent parent-offspring trios to discriminate between varied types of ASE (e.g., imprinting, genetic variation-dependent ASE, and random monoallelic expression (RME)). We show that the vast majority of ASE events are due to sequence-dependent genetic variant, which are evolutionarily conserved and may themselves play a cis-regulatory role. Particularly, 74% of non-RAD ASE events, even though they exhibit ASE biases toward the same parentally-inherited allele across different individuals, are derived from genetic variation but not imprinting. We further show that the RME effect may affect the effectiveness of the population-based method for detecting imprinting events and our pipeline can help to distinguish between these two ASE types. Taken together, this study provides a good indicator for categorization of different types of ASE, opening up this widespread and complex mechanism for comprehensive characterization.

Molecular interaction networks in the analyses of sequence variation and proteomics data.

PubMed

Stelzl, Ulrich

2013-12-01

Protein-protein interaction networks are typically generated in standard cell lines or model organisms as it is prohibitively difficult to record large interaction datasets from specific tissues or disease models at a reasonable pace. Although the interaction data are of high confidence, they thus do not reflect in vivo relationships as such. A wealth of physiologically relevant protein information, obtained under different conditions and from different systems, is available including information on genetic variation, protein levels, and PTMs. However, these data are difficult to assess comprehensively because the relationships between the entities remain elusive from the measurements. Here, we exemplarily highlight recent studies that gained deeper insight from genetic variation, protein, and PTM measurements using interaction information pointing toward the importance and potential of interaction networks for the interpretation of sequencing and proteomics data. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Candidate gene analyses of 3-dimensional dentoalveolar phenotypes in subjects with malocclusion

PubMed Central

Weaver, Cole A.; Miller, Steven F.; da Fontoura, Clarissa S. G.; Wehby, George L.; Amendt, Brad A.; Holton, Nathan E.; Allareddy, Veeratrishul; Southard, Thomas E.; Moreno Uribe, Lina M.

2017-01-01

Introduction Genetic studies of malocclusion etiology have identified 4 deleterious mutations in genes, DUSP6, ARHGAP21, FGF23, and ADAMTS1 in familial Class III cases. Although these variants may have large impacts on Class III phenotypic expression, their low frequency (<1%) makes them unlikely to explain most malocclusions. Thus, much of the genetic variation underlying the dentofacial phenotypic variation associated with malocclusion remains unknown. In this study, we evaluated associations between common genetic variations in craniofacial candidate genes and 3-dimensional dentoalveolar phenotypes in patients with malocclusion. Methods Pretreatment dental casts or cone-beam computed tomographic images from 300 healthy subjects were digitized with 48 landmarks. The 3-dimensional coordinate data were submitted to a geometric morphometric approach along with principal component analysis to generate continuous phenotypes including symmetric and asymmetric components of dentoalveolar shape variation, fluctuating asymmetry, and size. The subjects were genotyped for 222 single-nucleotide polymorphisms in 82 genes/loci, and phenotpye-genotype associations were tested via multivariate linear regression. Results Principal component analysis of symmetric variation identified 4 components that explained 68% of the total variance and depicted anteroposterior, vertical, and transverse dentoalveolar discrepancies. Suggestive associations (P < 0.05) were identified with PITX2, SNAI3, 11q22.2-q22.3, 4p16.1, ISL1, and FGF8. Principal component analysis for asymmetric variations identified 4 components that explained 51% of the total variations and captured left-to-right discrepancies resulting in midline deviations, unilateral crossbites, and ectopic eruptions. Suggestive associations were found with TBX1 AJUBA, SNAI3 SATB2, TP63, and 1p22.1. Fluctuating asymmetry was associated with BMP3 and LATS1. Associations for SATB2 and BMP3 with asymmetric variations remained significant after the Bonferroni correction (P <0.00022). Suggestive associations were found for centroid size, a proxy for dentoalveolar size variation with 4p16.1 and SNAI1. Conclusions Specific genetic pathways associated with 3-dimensional dentoalveolar phenotypic variation in malocclusions were identified. PMID:28257739

Species-Specific Variation in RELA Underlies Differences in NF-κB Activity: a Potential Role in African Swine Fever Pathogenesis▿

PubMed Central

Palgrave, Christopher J.; Gilmour, Linzi; Lowden, C. Stewart; Lillico, Simon G.; Mellencamp, Martha A.; Whitelaw, C. Bruce A.

2011-01-01

African swine fever virus (ASFV) is a highly infectious disease of domestic pigs, with virulent isolates causing a rapidly fatal hemorrhagic fever. In contrast, the porcine species endogenous to Africa tolerate infection. The ability of the virus to persist in one host while killing another genetically related host implies that disease severity may be, in part, modulated by host genetic variation. To complement transcription profiling approaches to identify the underlying genetic variation in the host response to ASFV, we have taken a candidate gene approach based on known signaling pathways that interact with the virus-encoded immunomodulatory protein A238L. We report the sequencing of these genes from different pig species and the identification and initial in vitro characterization of polymorphic variation in RELA (p65; v-rel reticuloendotheliosis viral oncogene homolog A), the major component of the NF-κB transcription factor. Warthog RELA and domestic pig RELA differ at three amino acids. Transient cell transfection assays indicate that this variation is reflected in reduced NF-κB activity in vitro for warthog RELA but not for domestic pig RELA. Induction assays indicate that warthog RELA and domestic pig RELA are elevated essentially to the same extent. Finally, mutational studies indicate that the S531P site conveys the majority of the functional variation between warthog RELA and domestic pig RELA. We propose that the variation in RELA identified between the warthog and domestic pig has the potential to underlie the difference between tolerance and rapid death upon ASFV infection. PMID:21450812

Ladybirds as Teaching Aids: 2. Potential for Practical and Project Work.

ERIC Educational Resources Information Center

Majerus, M. E. N.; And Others

1989-01-01

Presented are several ideas for projects involving ladybird beetles. Discussed is background information about the insects; and projects involving life histories, intra-specific variation, taxonomy, genetics, behavior, ecology, habitat surveys, population biology, and overwintering biology. Lists 12 references. (CW)

Genetic and Epigenetic Variations Induced by Wheat-Rye 2R and 5R Monosomic Addition Lines

PubMed Central

Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

2013-01-01

Background Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. Methodology/Principal Findings In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. Conclusions/Significance The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat. PMID:23342073

Genetic and epigenetic variations induced by wheat-rye 2R and 5R monosomic addition lines.

PubMed

Fu, Shulan; Sun, Chuanfei; Yang, Manyu; Fei, Yunyan; Tan, Feiqun; Yan, Benju; Ren, Zhenglong; Tang, Zongxiang

2013-01-01

Monosomic alien addition lines (MAALs) can easily induce structural variation of chromosomes and have been used in crop breeding; however, it is unclear whether MAALs will induce drastic genetic and epigenetic alterations. In the present study, wheat-rye 2R and 5R MAALs together with their selfed progeny and parental common wheat were investigated through amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) analyses. The MAALs in different generations displayed different genetic variations. Some progeny that only contained 42 wheat chromosomes showed great genetic/epigenetic alterations. Cryptic rye chromatin has introgressed into the wheat genome. However, one of the progeny that contained cryptic rye chromatin did not display outstanding genetic/epigenetic variation. 78 and 49 sequences were cloned from changed AFLP and MSAP bands, respectively. Blastn search indicated that almost half of them showed no significant similarity to known sequences. Retrotransposons were mainly involved in genetic and epigenetic variations. Genetic variations basically affected Gypsy-like retrotransposons, whereas epigenetic alterations affected Copia-like and Gypsy-like retrotransposons equally. Genetic and epigenetic variations seldom affected low-copy coding DNA sequences. The results in the present study provided direct evidence to illustrate that monosomic wheat-rye addition lines could induce different and drastic genetic/epigenetic variations and these variations might not be caused by introgression of rye chromatins into wheat. Therefore, MAALs may be directly used as an effective means to broaden the genetic diversity of common wheat.

Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough

PubMed Central

McMahon, George; Ring, Susan M.; Davey-Smith, George; Timpson, Nicholas J.

2015-01-01

Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. We carried out a case–control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E − 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. The majority of these associations were explained by the lead SNP rs9271768. Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy. PMID:26231221

Geographical genetic structuring and phenotypic variation in the Vellozia hirsuta (Velloziaceae) ochlospecies complex.

PubMed

Barbosa, Ariane R; Fiorini, Cecília F; Silva-Pereira, Viviane; Mello-Silva, Renato; Borba, Eduardo L

2012-09-01

Vellozia hirsuta forms a complex presenting wide morphological and anatomical variation, resulting in five specific names and 14 morpho-anatomical patterns occurring in disjunct populations. We carried out a phylogeographical study to investigate the existence of correlation among the genetic and morphological patterns within this complex, and to determine whether it is composed of various species or should be treated as an ochlospecies, a species having widely polymorphic and weakly polytypic complex variation, with morphological characteristics varying independently. We carried out phylogeographical analyses using cpDNA rpl32F-trnL intergenic region. We found 20 haplotypes in 23 populations sampled. The populations are genetically structured (Φ(ST) = 0.818) into four phylogeographical groups demonstrating geographical structuring but with no correlation with morpho-anatomical patterns. Our analyses do not support recognizing any of the species now synonymized under Vellozia hirsuta. The northern populations were the most genetically differentiated and could be considered a distinct taxon, as they are also morphologically different. It is recommended that Vellozia hirsuta be considered a single enormously variable species. The patterns of variation within V. hirsuta probably are related to climatic changes that occurred during the Pleistocene Epoch in tropical Brazil when reductions in forest cover favored the expansion of V. hirsuta populations into extensive lowland areas. The expansion of forest cover at the end of the glaciations would have again restricted the occurrence of campos rupestres vegetation to high elevations, which constitute the current centers of diversity of this species.

Genetic variation affecting host-parasite interactions: different genes affect different aspects of sigma virus replication and transmission in Drosophila melanogaster.

PubMed

Bangham, Jenny; Kim, Kang-Wook; Webster, Claire L; Jiggins, Francis M

2008-04-01

In natural populations, genetic variation affects resistance to disease. Knowing how much variation exists, and understanding the genetic architecture of this variation, is important for medicine, for agriculture, and for understanding evolutionary processes. To investigate the extent and nature of genetic variation affecting resistance to pathogens, we are studying a tractable model system: Drosophila melanogaster and its natural pathogen the vertically transmitted sigma virus. We show that considerable genetic variation affects transmission of the virus from parent to offspring. However, maternal and paternal transmission of the virus is affected by different genes. Maternal transmission is a simple Mendelian trait: most of the genetic variation is explained by a polymorphism in ref(2)P, a gene already well known to affect resistance to sigma. In contrast, there is considerable genetic variation in paternal transmission that cannot be explained by ref(2)P and is caused by other loci on chromosome 2. Furthermore, we found no genetic correlation between paternal transmission of the virus and resistance to infection by the sigma virus following injection. This suggests that different loci affect viral replication and paternal transmission.

A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

PubMed

Castellanos, Elisabeth; Gel, Bernat; Rosas, Inma; Tornero, Eva; Santín, Sheila; Pluvinet, Raquel; Velasco, Juan; Sumoy, Lauro; Del Valle, Jesús; Perucho, Manuel; Blanco, Ignacio; Navarro, Matilde; Brunet, Joan; Pineda, Marta; Feliubadaló, Lidia; Capellá, Gabi; Lázaro, Conxi; Serra, Eduard

2017-01-04

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.

Genetic variation in natural honeybee populations, Apis mellifera capensis

NASA Astrophysics Data System (ADS)

Hepburn, Randall; Neumann, Peter; Radloff, Sarah E.

2004-09-01

Genetic variation in honeybee, Apis mellifera, populations can be considerably influenced by breeding and commercial introductions, especially in areas with abundant beekeeping. However, in southern Africa apiculture is based on the capture of wild swarms, and queen rearing is virtually absent. Moreover, the introduction of European subspecies constantly failed in the Cape region. We therefore hypothesize a low human impact on genetic variation in populations of Cape honeybees, Apis mellifera capensis. A novel solution to studying genetic variation in honeybee populations based on thelytokous worker reproduction is applied to test this hypothesis. Environmental effects on metrical morphological characters of the phenotype are separated to obtain a genetic residual component. The genetic residuals are then re-calculated as coefficients of genetic variation. Characters measured included hair length on the abdomen, width and length of wax plate, and three wing angles. The data show for the first time that genetic variation in Cape honeybee populations is independent of beekeeping density and probably reflects naturally occurring processes such as gene flow due to topographic and climatic variation on a microscale.

Estimation and Partitioning of Heritability in Human Populations using Whole Genome Analysis Methods

PubMed Central

Vinkhuyzen, Anna AE; Wray, Naomi R; Yang, Jian; Goddard, Michael E; Visscher, Peter M

2014-01-01

Understanding genetic variation of complex traits in human populations has moved from the quantification of the resemblance between close relatives to the dissection of genetic variation into the contributions of individual genomic loci. But major questions remain unanswered: how much phenotypic variation is genetic, how much of the genetic variation is additive and what is the joint distribution of effect size and allele frequency at causal variants? We review and compare three whole-genome analysis methods that use mixed linear models (MLM) to estimate genetic variation, using the relationship between close or distant relatives based on pedigree or SNPs. We discuss theory, estimation procedures, bias and precision of each method and review recent advances in the dissection of additive genetic variation of complex traits in human populations that are based upon the application of MLM. Using genome wide data, SNPs account for far more of the genetic variation than the highly significant SNPs associated with a trait, but they do not account for all of the genetic variance estimated by pedigree based methods. We explain possible reasons for this ‘missing’ heritability. PMID:23988118

Does advertisement call variation coincide with genetic variation in the genetically diverse frog taxon currently known as Leptodactylus fuscus (Amphibia: Leptodactylidae)?

PubMed

Heyer, W Ronald; Reid, Yana R

2003-03-01

The frog Leptodactylus fuscus is found throughout much of South America in open and disturbed habitats. Previous study of genetic differentiation in L. fuscus demonstrated that there was lack of genetic exchange among population units consistent with multiple species, rather than a single species. We examine advertisement vocalizations of L. fuscus to determine whether call variation coincides with genetic differentiation. Calls were analyzed for 32 individual frogs from 25 localities throughout the distributional range of L. fuscus. Although there is variation in calls among geographic samples, call variation is not concordant with genetic variation or geographic distance and the call variation observed is less than that typically found among other closely related species of Leptodactylus. This study is an example of the rare pattern of strong genetic differentiation unaccompanied by salient differences in advertisement calls. The relative infrequency of this pattern as currently understood may only reflect the lack of detailed analyses of genetic and acoustic differentiation within population systems currently understood as single species with substantial geographic distributions.

Sex reduces genetic variation: a multidisciplinary review.

PubMed

Gorelick, Root; Heng, Henry H Q

2011-04-01

For over a century, the paradigm has been that sex invariably increases genetic variation, despite many renowned biologists asserting that sex decreases most genetic variation. Sex is usually perceived as the source of additive genetic variance that drives eukaryotic evolution vis-à-vis adaptation and Fisher's fundamental theorem. However, evidence for sex decreasing genetic variation appears in ecology, paleontology, population genetics, and cancer biology. The common thread among many of these disciplines is that sex acts like a coarse filter, weeding out major changes, such as chromosomal rearrangements (that are almost always deleterious), but letting minor variation, such as changes at the nucleotide or gene level (that are often neutral), flow through the sexual sieve. Sex acts as a constraint on genomic and epigenetic variation, thereby limiting adaptive evolution. The diverse reasons for sex reducing genetic variation (especially at the genome level) and slowing down evolution may provide a sufficient benefit to offset the famed costs of sex. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Identification of Novel Genetic Markers of Breast Cancer Survival

PubMed Central

Guo, Qi; Schmidt, Marjanka K.; Kraft, Peter; Canisius, Sander; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Kar, Siddhartha; Beesley, Jonathan; Dunning, Alison M.; Shah, Mitul; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Lambrechts, Diether; Weltens, Caroline; Leunen, Karin; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Blomqvist, Carl; Aittomäki, Kristiina; Fagerholm, Rainer; Muranen, Taru A.; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Broeks, Annegien; Hogervorst, Frans B.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; van den Ouweland, Ans M. W.; Marme, Federik; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Holleczek, Bernd; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Li, Jingmei; Brand, Judith S.; Humphreys, Keith; Devilee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Mariani, Paolo; Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ekici, Arif B.; Chenevix-Trench, Georgia; Balleine, Rosemary; Phillips, Kelly-Anne; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Hamann, Ute; Kabisch, Maria; Ulmer, Hans Ulrich; Rüdiger, Thomas; Margolin, Sara; Kristensen, Vessela; Nord, Silje; Evans, D. Gareth; Abraham, Jean E.; Earl, Helena M.; Hiller, Louise; Dunn, Janet A.; Bowden, Sarah; Berg, Christine; Campa, Daniele; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Hankinson, Susan E.; Hoover, Robert N.; Hüsing, Anika; Kaaks, Rudolf; Machiela, Mitchell J.; Willett, Walter; Barrdahl, Myrto; Canzian, Federico; Chin, Suet-Feung; Caldas, Carlos; Hunter, David J.; Lindstrom, Sara; García-Closas, Montserrat; Hall, Per; Easton, Douglas F.; Eccles, Diana M.; Rahman, Nazneen; Nevanlinna, Heli; Pharoah, Paul D. P.

2015-01-01

Background: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer–specific survival. Methods: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)–negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. Results: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10–8). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. Conclusions: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors. PMID:25890600

Extensive interbreeding occurred among multiple matriarchal ancestors during the domestication of dogs: evidence from inter- and intraspecies polymorphisms in the D-loop region of mitochondrial DNA between dogs and wolves.

PubMed

Tsuda, K; Kikkawa, Y; Yonekawa, H; Tanabe, Y

1997-08-01

To test the hypothesis that the domestic dogs are derived from several different ancestral gray wolf populations, we compared the sequence of the displacement (D)-loop region of the mitochondrial DNA (mtDNA) from 24 breeds of domestic dog (34 individual dogs) and 3 subspecies of gray wolf (Canis lupus lupus, C.l. pallipes and C.l. chanco; 19 individuals). The intraspecific sequence variations within domestic dogs (0.00-3.19%) and within wolves (0.00-2.88%) were comparable to the interspecific variations between domestic dogs and wolves (0.30-3.35%). A repetitive sequence with repeat units (TACACGTA/GCG) that causes the size variation in the D-loop region was also found in both dogs and wolves. However, no nucleotide substitutions or repetitive arrays were specific for domestic dogs or for wolves. These results showed that there is a close genetic relationship between dogs and wolves. Two major clades appeared in the phylogenetic trees constructed by neighbor-joining and by the maximum parsimony method; one clade containing Chinese wolf (C.l. chanco) showed extensive variations while the other showed only slight variation. This showed that there were two major genetic components both in domestic dogs and in wolves. However, neither clades nor haplotypes specific for any dog breed were observed, whereas subspecies-specific clades were found in Asiatic wolves. These results suggested that the extant breeds of domestic dogs have maintained a large degree of mtDNA polymorphisms introduced from their ancestral wolf populations, and that extensive interbreedings had occurred among multiple matriarchal origins.

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians.

PubMed

Scott, William R; Zhang, Weihua; Loh, Marie; Tan, Sian-Tsung; Lehne, Benjamin; Afzal, Uzma; Peralta, Juan; Saxena, Richa; Ralhan, Sarju; Wander, Gurpreet S; Bozaoglu, Kiymet; Sanghera, Dharambir K; Elliott, Paul; Scott, James; Chambers, John C; Kooner, Jaspal S

2016-01-01

South Asians are 1/4 of the world's population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10-6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans.

Investigation of Genetic Variation Underlying Central Obesity amongst South Asians

PubMed Central

Scott, William R.; Zhang, Weihua; Loh, Marie; Tan, Sian-Tsung; Lehne, Benjamin; Afzal, Uzma; Peralta, Juan; Saxena, Richa; Ralhan, Sarju; Wander, Gurpreet S.; Bozaoglu, Kiymet; Sanghera, Dharambir K.; Elliott, Paul; Scott, James; Chambers, John C.; Kooner, Jaspal S.

2016-01-01

South Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our findings argue against an important contribution for population-specific or cosmopolitan genetic variants underlying the increased risk of central obesity in South Asians compared to Europeans. PMID:27195708

Genetic Risk Score of NOS Gene Variants Associated with Myocardial Infarction Correlates with Coronary Incidence across Europe

PubMed Central

Carreras-Torres, Robert; Kundu, Suman; Zanetti, Daniela; Esteban, Esther

2014-01-01

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65–85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition. PMID:24806096

DNA methylation profiling reveals the presence of population-specific signatures correlating with phenotypic characteristics.

PubMed

Giri, Anil K; Bharadwaj, Soham; Banerjee, Priyanka; Chakraborty, Shraddha; Parekatt, Vaisak; Rajashekar, Donaka; Tomar, Abhishek; Ravindran, Aarthi; Basu, Analabha; Tandon, Nikhil; Bharadwaj, Dwaipayan

2017-06-01

Phenotypic characteristics are known to vary substantially among different ethnicities around the globe. These variations are mediated by number of stochastic events and cannot be attributed to genetic architecture alone. DNA methylation is a well-established mechanism that sculpts our epigenome influencing phenotypic variation including disease manifestation. Since DNA methylation is an important determinant for health issues of a population, it demands a thorough investigation of the natural differences in genome wide DNA methylation patterns across different ethnic groups. This study is based on comparative analyses of methylome from five different ethnicities with major focus on Indian subjects. The current study uses hierarchical clustering approaches, principal component analysis and locus specific differential methylation analysis on Illumina 450K methylation data to compare methylome of different ethnic subjects. Our data indicates that the variations in DNA methylation patterns of Indians are less among themselves compared to other global population. It empirically correlated with dietary, cultural and demographical divergences across different ethnic groups. Our work further suggests that Indians included in this study, despite their genetic similarity with the Caucasian population, are in close proximity with Japanese in terms of their methylation signatures.

Climatic niche and neutral genetic diversity of the six Iberian pine species: a retrospective and prospective view.

PubMed

Soto, A; Robledo-Arnuncio, J J; González-Martínez, S C; Smouse, P E; Alía, R

2010-04-01

Quaternary climatic fluctuations have left contrasting historical footprints on the neutral genetic diversity patterns of existing populations of different tree species. We should expect the demography, and consequently the neutral genetic structure, of taxa less tolerant to particular climatic extremes to be more sensitive to long-term climate fluctuations. We explore this hypothesis here by sampling all six pine species found in the Iberian Peninsula (2464 individuals, 105 populations), using a common set of chloroplast microsatellite markers, and by looking at the association between neutral genetic diversity and species-specific climatic requirements. We found large variation in neutral genetic diversity and structure among Iberian pines, with cold-enduring mountain species (Pinus uncinata, P. sylvestris and P. nigra) showing substantially greater diversity than thermophilous taxa (P. pinea and P. halepensis). Within species, we observed a significant positive correlation between population genetic diversity and summer precipitation for some of the mountain pines. The observed pattern is consistent with the hypotheses that: (i) more thermophilous species have been subjected to stronger demographic fluctuations in the past, as a consequence of their maladaptation to recurrent glacial cold stages; and (ii) altitudinal migrations have allowed the maintenance of large effective population sizes and genetic variation in cold-tolerant species, especially in more humid regions. In the light of these results and hypotheses, we discuss some potential genetic consequences of impending climate change.

Inter Individual Variations of the Fish Skin Microbiota: Host Genetics Basis of Mutualism?

PubMed Central

Boutin, Sébastien; Sauvage, Christopher; Bernatchez, Louis; Audet, Céline; Derome, Nicolas

2014-01-01

The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL) associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens. PMID:25068850

Inter individual variations of the fish skin microbiota: host genetics basis of mutualism?

PubMed

Boutin, Sébastien; Sauvage, Christopher; Bernatchez, Louis; Audet, Céline; Derome, Nicolas

2014-01-01

The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL) associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens.

Facing the facts: The Runx2 gene is associated with variation in facial morphology in primates.

PubMed

Ritzman, Terrence B; Banovich, Nicholas; Buss, Kaitlin P; Guida, Jennifer; Rubel, Meagan A; Pinney, Jennifer; Khang, Bao; Ravosa, Matthew J; Stone, Anne C

2017-10-01

The phylogenetic and adaptive factors that cause variation in primate facial form-including differences among the major primate clades and variation related to feeding and/or social behavior-are relatively well understood. However, comparatively little is known about the genetic mechanisms that underlie diversity in facial form in primates. Because it is essential for osteoblastic differentiation and skeletal development, the runt-related transcription factor 2 (Runx2) is one gene that may play a role in these genetic mechanisms. Specifically, polymorphisms in the QA ratio (determined by the ratio of the number of polyglutamines to polyalanines in one functional domain of Runx2) have been shown to be correlated with variation in facial length and orientation in other mammal groups. However, to date, the relationship between variation in this gene and variation in facial form in primates has not been explicitly tested. To test the hypothesis that the QA ratio is correlated with facial form in primates, the current study quantified the QA ratio, facial length, and facial angle in a sample of 33 primate species and tested for correlation using phylogenetic generalized least squares. The results indicate that the QA ratio of the Runx2 gene is positively correlated with variation in relative facial length in anthropoid primates. However, no correlation was found in strepsirrhines, and there was no correlation between facial angle and the QA ratio in any groups. These results suggest that, in primates, the QA ratio of the Runx2 gene may play a role in modulating facial size, but not facial orientation. This study therefore provides important clues about the genetic and developmental mechanisms that may underlie variation in facial form in primates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic Variation and Structure in Contrasting Geographic Distributions: Widespread Versus Restricted Black-Tailed Prairie Dogs (Subgenus Cynomys).

PubMed

Castellanos-Morales, Gabriela; Ortega, Jorge; Castillo-Gámez, Reyna A; Sackett, Loren C; Eguiarte, Luis E

2015-01-01

Species of restricted distribution are considered more vulnerable to extinction because of low levels of genetic variation relative to widespread taxa. Species of the subgenus Cynomys are an excellent system to compare genetic variation and degree of genetic structure in contrasting geographic distributions. We assessed levels of genetic variation, genetic structure, and genetic differentiation in widespread Cynomys ludovicianus and restricted C. mexicanus using 1997bp from the cytochrome b and control region (n = 223 C. ludovicianus; 77 C. mexicanus), and 10 nuclear microsatellite loci (n = 207 and 78, respectively). Genetic variation for both species was high, and genetic structure in the widespread species was higher than in the restricted species. C. mexicanus showed values of genetic variation, genetic structure, and genetic differentiation similar to C. ludovicianus at smaller geographic scales. Results suggest the presence of at least 2 historical refuges for C. ludovicianus and that the Sierra Madre Occidental represents a barrier to gene flow. Chihuahua and New Mexico possess high levels of genetic diversity and should be protected, while Sonora should be treated as an independent management unit. For C. mexicanus, connectivity among colonies is very important and habitat fragmentation and habitat loss should be mitigated to maintain gene flow. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparative Agronomic Performance and Reaction to Fusarium wilt of Lens culinaris × L. orientalis and L. culinaris × L. ervoides derivatives.

PubMed

Singh, Mohar; Rana, Jai C; Singh, Badal; Kumar, Sandeep; Saxena, Deep R; Saxena, Ashok; Rizvi, Aqeel H; Sarker, Ashutosh

2017-01-01

The development of transgressive phenotype in the segregating populations has been speculated to contribute to niche divergence of hybrid lineages, which occurs most frequently at larger genetic distances. Wild Lens species are considered to be more resistant against major biotic and abiotic stresses than that of the cultivated species. In the present study, we assessed the comparative agronomic performance of lentil ( Lens culinaris subsp. culinaris ) inter-sub-specific ( L. culinaris subsp. orientalis ) and interspecific ( L. ervoides ) derivatives, also discussed its probable basis of occurrence. The F 3 , F 4 , and F 5 inter sub-specific and interspecific populations of ILL8006 × ILWL62 and ILL10829 × ILWL30, respectively revealed a substantial range of variation for majority of agro-morphological traits as reflected by the range, mean and coefficient of variation. A high level of fruitful heterosis was also observed in F 3 and F 4 progeny for important traits of interest. Phenotypic coefficient of variation (PCV) was higher in magnitude than genotypic coefficient of variation (GCV) in all generations for several quantitative characters. The results showed high heritability estimates for majority of traits in conjunction with low to high genetic advance in F 3 and F 4 generations. Further, F 5 progeny of ILL10829 × ILWL30, manifested resistant disease reaction for fifteen recombinant inbred lines (RILs) against ( Fusarium oxysporum f. sp. lentis ( Vasd. Srin .) Gord.). The multilocation agronomic evaluation of both crosses showed better results for earliness, desirable seed yield and Fusarium wilt resistance under two agro-ecological regions of north-western India. These better performing recombinants of ILL8006 × ILWL62 and ILL10829 × ILWL30 can be advanced for further genetic improvement and developing high yielding disease resistant cultivars of lentil.

Colonizing the world in spite of reduced MHC variation

USGS Publications Warehouse

Gangoso, L.; Alcaide, M.; Grande, J.M.; Muñoz, J.; Talbot, Sandra L.; Sonsthagen, Sarah A.; Sage, Kevin; Figuerola, J.

2012-01-01

Reduced immune gene diversity is thought to negatively affect the capacity of organisms to adapt to pathogen challenges, which represent a major force in natural selection. Genes of the Major Histocompatibility Complex (MHC) are the most widely invoked adaptive loci in conservation biology, and have become the most popular genetic markers to investigate pathogen-host interactions in vertebrates. Although MHC genes are the most polymorphic genes described in the vertebrate genome, the extent to which MHC diversity determines the long-term persistence of populations is, unclear and often debated, as recent studies have documented the occurrence of natural populations thriving even after a depletion of MHC diversity caused by genetic drift. Here, we show that some phylogenetically related species belonging to the Falco genus (Aves: Falconidae) present a dramatically low MHC variability that has not precluded, nevertheless, the successful colonization of almost all existing regions and habitats worldwide. We found evidence for two remarkably different patterns of MHC variation within the genus. While kestrels show a high MHC variation according to the general theory, falcons exhibit an ancestrally low intra- and inter-specific MHC allelic diversity. We provide compelling evidence that this pattern is not caused by the degeneration of functional genes into pseudogenes, the inadvertent analyses of paralogous MHC genes, or the devastating action of genetic drift. Instead, our results strongly support the idea of an evolutionary transition driven and maintained by natural selection from primarily highly variable towards low polymorphic, but functional and expressed, MHC genes with species-specific pathogen-recognition capabilities.

Population structure of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Thailand based on PCR-RAPD markers.

PubMed

Thaenkham, Urusa; Pakdee, Wallop; Nuamtanong, Supaporn; Maipanich, Wanna; Pubampen, Somchit; Sa-Nguankiat, Surapol; Komalamisra, Chalit

2012-05-01

Angiostrongylus cantonensis is the causative agent of angiostrongyliasis, which is widely distributed throughout the world. It can specifically infect many species of intermediate and definitive hosts. This study examined the genetic differentiation and population structure using the RAPD-PCR method of parasites obtained from 8 different geographical areas of Thailand. Based on 8 primers, high levels of genetic diversity and low levels of gene flow among populations were found. Using genetic distance and neighbor-joining dendrogram methods, A. cantonensis in Thailand could be divided into two groups with statistically significant genetic differentiation of the two populations. However, genotypic variations and haplotype relationships need to be further elucidated using other markers.

Associations between race, sex and immune response variations to rubella vaccination in two independent cohorts

PubMed Central

Haralambieva, Iana H.; Salk, Hannah M.; Lambert, Nathaniel D.; Ovsyannikova, Inna G.; Kennedy, Richard B.; Warner, Nathaniel D.; Pankratz, V.Shane; Poland, Gregory A.

2014-01-01

Introduction Immune response variations after vaccination are influenced by host genetic factors and demographic variables, such as race, ethnicity and sex. The latter have not been systematically studied in regard to live rubella vaccine, but are of interest for developing next generation vaccines for diverse populations, for predicting immune responses after vaccination, and for better understanding the variables that impact immune response. Methods We assessed associations between demographic variables, including race, ethnicity and sex, and rubella-specific neutralizing antibody levels and secreted cytokines (IFN! , IL-6) in two independent cohorts (1,994 subjects), using linear and linear mixed models approaches, and genetically defined racial and ethnic categorizations. Results Our replicated findings in two independent, large, racially diverse cohorts indicate that individuals of African descent have significantly higher rubella-specific neutralizing antibody levels compared to individuals of European descent and/or Hispanic ethnicity (p! 0.001). Conclusion Our study provides consistent evidence for racial/ethnic differences in humoral immune response following rubella vaccination. PMID:24530932

Germline Mutations and Polymorphisms in the Origins of Cancers in Women

PubMed Central

Hirshfield, Kim M.; Rebbeck, Timothy R.; Levine, Arnold J.

2010-01-01

Several female malignancies including breast, ovarian, and endometrial cancers can be characterized based on known somatic and germline mutations. Initiation and propagation of tumors reflect underlying genomic alterations such as mutations, polymorphisms, and copy number variations found in genes of multiple cellular pathways. The contributions of any single genetic variation or mutation in a population depend on its frequency and penetrance as well as tissue-specific functionality. Genome wide association studies, fluorescence in situ hybridization, comparative genomic hybridization, and candidate gene studies have enumerated genetic contributors to cancers in women. These include p53, BRCA1, BRCA2, STK11, PTEN, CHEK2, ATM, BRIP1, PALB2, FGFR2, TGFB1, MDM2, MDM4 as well as several other chromosomal loci. Based on the heterogeneity within a specific tumor type, a combination of genomic alterations defines the cancer subtype, biologic behavior, and in some cases, response to therapeutics. Consideration of tumor heterogeneity is therefore important in the critical analysis of gene associations in cancer. PMID:20111735

Temporal differentiation across a West-European Y-chromosomal cline: genealogy as a tool in human population genetics

PubMed Central

Larmuseau, Maarten HD; Ottoni, Claudio; Raeymaekers, Joost AM; Vanderheyden, Nancy; Larmuseau, Hendrik FM; Decorte, Ronny

2012-01-01

The pattern of population genetic variation and allele frequencies within a species are unstable and are changing over time according to different evolutionary factors. For humans, it is possible to combine detailed patrilineal genealogical records with deep Y-chromosome (Y-chr) genotyping to disentangle signals of historical population genetic structures because of the exponential increase in genetic genealogical data. To test this approach, we studied the temporal pattern of the ‘autochthonous' micro-geographical genetic structure in the region of Brabant in Belgium and the Netherlands (Northwest Europe). Genealogical data of 881 individuals from Northwest Europe were collected, from which 634 family trees showed a residence within Brabant for at least one generation. The Y-chr genetic variation of the 634 participants was investigated using 110 Y-SNPs and 38 Y-STRs and linked to particular locations within Brabant on specific time periods based on genealogical records. Significant temporal variation in the Y-chr distribution was detected through a north–south gradient in the frequencies distribution of sub-haplogroup R1b1b2a1 (R-U106), next to an opposite trend for R1b1b2a2g (R-U152). The gradient on R-U106 faded in time and even became totally invisible during the Industrial Revolution in the first half of the nineteenth century. Therefore, genealogical data for at least 200 years are required to study small-scale ‘autochthonous' population structure in Western Europe. PMID:22126748

Genetic Variability of the Neogregarine Apicystis bombi, an Etiological Agent of an Emergent Bumblebee Disease

PubMed Central

Maebe, Kevin; Arbetman, Marina; Morales, Carolina; Graystock, Peter; Hughes, William O. H.; Plischuk, Santiago; Lange, Carlos E.; de Graaf, Dirk C.; Zapata, Nelson; de la Rosa, Jose Javier Perez; Murray, Tomás E.; Brown, Mark J. F.; Smagghe, Guy

2013-01-01

The worldwide spread of diseases is considered a major threat to biodiversity and a possible driver of the decline of pollinator populations, particularly when novel species or strains of parasites emerge. Previous studies have suggested that populations of introduced European honeybee (Apis mellifera) and bumblebee species (Bombus terrestris and Bombus ruderatus) in Argentina share the neogregarine parasite Apicystis bombi with the native bumblebee (Bombus dahlbomii). In this study we investigated whether A. bombi is acting as an emergent parasite in the non-native populations. Specifically, we asked whether A. bombi, recently identified in Argentina, was introduced by European, non-native bees. Using ITS1 and ITS2 to assess the parasite’s intraspecific genetic variation in bees from Argentina and Europe, we found a largely unstructured parasite population, with only 15% of the genetic variation being explained by geographic location. The most abundant haplotype in Argentina (found in all 9 specimens of non-native species) was identical to the most abundant haplotype in Europe (found in 6 out of 8 specimens). Similarly, there was no evidence of structuring by host species, with this factor explaining only 17% of the genetic variation. Interestingly, parasites in native Bombus ephippiatus from Mexico were genetically distant from the Argentine and European samples, suggesting that sufficient variability does exist in the ITS region to identify continent-level genetic structure in the parasite. Thus, the data suggest that A. bombi from Argentina and Europe share a common, relatively recent origin. Although our data did not provide information on the direction of transfer, the absence of genetic structure across space and host species suggests that A. bombi may be acting as an emergent infectious disease across bee taxa and continents. PMID:24324696

Beyond thriftiness: Independent and interactive effects of genetic and dietary factors on variations in fat deposition and distribution across populations

PubMed Central

Casazza, Krista; Beasley, T. Mark; Fernandez, Jose R.

2011-01-01

The thrifty genotype hypothesis initiated speculation that feast and famine cycling throughout history may have led to group-specific alterations of the human genome, thereby augmenting the capacity for excessive fat mass accrual when immersed in the modern-day obesogenic environment. Contemporary work, however, suggests alternative mechanisms influencing fuel utilization and subsequent tissue partitioning to be more relevant in the etiology of population-based variation in adipose storage. The objective of this study was to evaluate the independent and interactive contribution of ancestral admixture as a proxy for population-based genetic variation and diet on adipose tissue deposition and distribution in peripubertal children and to identify differences in racial/ethnic and sex groups. Two-hundred seventy-eight children (53% male) aged 7–12y, categorized by parental self-report as African- (n=91), European- (n=110), or Hispanic American (n=77), participated. Ancestral genetic admixture was estimated using 140 ancestry informative markers. Body composition was evaluated by dual-energy x-ray absorptiometry; energy expenditure by indirect calorimetry and accelerometry; and diet by 24h–recall. Admixture independently contributed to all adiposity parameters; i.e., estimates of European and Amerindian ancestries were positively associated with all adiposity parameters, whereas African genetic admixture was inversely associated with adiposity. In boys, energy intake was associated with adiposity, irrespective of macronutrient profile, whereas in girls, the relationship was mediated by carbohydrate. We also observed moderating effects of energy balance/fuel utilization of the interaction between ancestral genetic admixture and diet. Interactive effects of genetic and non-genetic factors alter metabolic pathways and underlie some of the present population-based differences in fat storage. PMID:21365611

Geographic distribution of haplotype diversity at the bovine casein locus

PubMed Central

Jann, Oliver C; Ibeagha-Awemu, Eveline M; Özbeyaz, Ceyhan; Zaragoza, Pilar; Williams, John L; Ajmone-Marsan, Paolo; Lenstra, Johannes A; Moazami-Goudarzi, Katy; Erhardt, Georg

2004-01-01

The genetic diversity of the casein locus in cattle was studied on the basis of haplotype analysis. Consideration of recently described genetic variants of the casein genes which to date have not been the subject of diversity studies, allowed the identification of new haplotypes. Genotyping of 30 cattle breeds from four continents revealed a geographically associated distribution of haplotypes, mainly defined by frequencies of alleles at CSN1S1 and CSN3. The genetic diversity within taurine breeds in Europe was found to decrease significantly from the south to the north and from the east to the west. Such geographic patterns of cattle genetic variation at the casein locus may be a result of the domestication process of modern cattle as well as geographically differentiated natural or artificial selection. The comparison of African Bos taurus and Bos indicus breeds allowed the identification of several Bos indicus specific haplotypes (CSN1S1*C-CSN2*A2-CSN3*AI/CSN3*H) that are not found in pure taurine breeds. The occurrence of such haplotypes in southern European breeds also suggests that an introgression of indicine genes into taurine breeds could have contributed to the distribution of the genetic variation observed. PMID:15040901

Interactions between genetic variation and cellular environment in skeletal muscle gene expression.

PubMed

Taylor, D Leland; Knowles, David A; Scott, Laura J; Ramirez, Andrea H; Casale, Francesco Paolo; Wolford, Brooke N; Guan, Li; Varshney, Arushi; Albanus, Ricardo D'Oliveira; Parker, Stephen C J; Narisu, Narisu; Chines, Peter S; Erdos, Michael R; Welch, Ryan P; Kinnunen, Leena; Saramies, Jouko; Sundvall, Jouko; Lakka, Timo A; Laakso, Markku; Tuomilehto, Jaakko; Koistinen, Heikki A; Stegle, Oliver; Boehnke, Michael; Birney, Ewan; Collins, Francis S

2018-01-01

From whole organisms to individual cells, responses to environmental conditions are influenced by genetic makeup, where the effect of genetic variation on a trait depends on the environmental context. RNA-sequencing quantifies gene expression as a molecular trait, and is capable of capturing both genetic and environmental effects. In this study, we explore opportunities of using allele-specific expression (ASE) to discover cis-acting genotype-environment interactions (GxE)-genetic effects on gene expression that depend on an environmental condition. Treating 17 common, clinical traits as approximations of the cellular environment of 267 skeletal muscle biopsies, we identify 10 candidate environmental response expression quantitative trait loci (reQTLs) across 6 traits (12 unique gene-environment trait pairs; 10% FDR per trait) including sex, systolic blood pressure, and low-density lipoprotein cholesterol. Although using ASE is in principle a promising approach to detect GxE effects, replication of such signals can be challenging as validation requires harmonization of environmental traits across cohorts and a sufficient sampling of heterozygotes for a transcribed SNP. Comprehensive discovery and replication will require large human transcriptome datasets, or the integration of multiple transcribed SNPs, coupled with standardized clinical phenotyping.

Climatic suitability, isolation by distance and river resistance explain genetic variation in a Brazilian whiptail lizard.

PubMed

Oliveira, Eliana Faria; Martinez, Pablo Ariel; São-Pedro, Vinícius Avelar; Gehara, Marcelo; Burbrink, Frank Thomas; Mesquita, Daniel Oliveira; Garda, Adrian Antonio; Colli, Guarino Rinaldi; Costa, Gabriel Correa

2018-03-01

Spatial patterns of genetic variation can help understand how environmental factors either permit or restrict gene flow and create opportunities for regional adaptations. Organisms from harsh environments such as the Brazilian semiarid Caatinga biome may reveal how severe climate conditions may affect patterns of genetic variation. Herein we combine information from mitochondrial DNA with physical and environmental features to study the association between different aspects of the Caatinga landscape and spatial genetic variation in the whiptail lizard Ameivula ocellifera. We investigated which of the climatic, environmental, geographical and/or historical components best predict: (1) the spatial distribution of genetic diversity, and (2) the genetic differentiation among populations. We found that genetic variation in A. ocellifera has been influenced mainly by temperature variability, which modulates connectivity among populations. Past climate conditions were important for shaping current genetic diversity, suggesting a time lag in genetic responses. Population structure in A. ocellifera was best explained by both isolation by distance and isolation by resistance (main rivers). Our findings indicate that both physical and climatic features are important for explaining the observed patterns of genetic variation across the xeric Caatinga biome.

Genetic variation in California oaks

Treesearch

Constance I. Millar; Diane L. Delany; Lawrence A. Riggs

1990-01-01

In forestry the importance of genetic variation for successful reproduction, survival and growth has been widely documented for commercial conifers; until recently, little genetic work has been done on the California oaks. Even before the nature of genetic variation was scientifically investigated, its importance was suspected in operational forestry. Many failures of...

Conservation genetics of bull trout: Geographic distribution of variation at microsatellite loci.

Treesearch

P. Spruell; A.R. Hemmingsen; P.J. Howell; N. Kanda; F.W. Allendorf

2003-01-01

We describe the genetic population structure of 65 bull trout (Salvelinus confluentus) populations from the northwestern United States using four microsatellite loci. The distribution of genetic variation as measured by microsatellites is consistent with previous allozyme and mitochondrial DNA analysis. There is relatively little genetic variation...

G-Protein Genomic Association With Normal Variation in Gray Matter Density

PubMed Central

Chen, Jiayu; Calhoun, Vince D.; Arias-Vasquez, Alejandro; Zwiers, Marcel P.; van Hulzen, Kimm; Fernández, Guillén; Fisher, Simon E.; Franke, Barbara; Turner, Jessica A.; Liu, Jingyu

2017-01-01

While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = −0.16, P = 2.34 × 10−8), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = −0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions. PMID:26248772

Pharmacogenetics of drug response in Parkinson's disease.

PubMed

Džoljić, Eleonora; Novaković, Ivana; Krajinovic, Maja; Grbatinić, Ivan; Kostić, Vladimir

2015-01-01

Parkinson's disease (PD) is a debilitating, demoralizing and financially devastating condition affecting 1% of population at the age of 60 years. Thus, very important issue to address is individual therapy optimization. Recent results have shown evidence that variable efficacy of treatment and risk of motor and mental complications could have genetic origin. Significant roles in that process play (pharmaco)genomic/genetic studies of PD. Variability in genes coding for drug-metabolizing enzymes, drug receptors and proteins involved in drug pathway signaling is an important factor determining inter-individual variability in drug responses. Interpersonal differences in drug responses are clearly documented although individualized treatment of PD is not widely known. Treatment with antiparkinsonian drugs is associated with the development of complications, such as L-DOPA-induced dyskinesia (LID), hallucinations and excessive daytime sleepiness. Carriers of specific genetic polymorphisms are particularly susceptible to development of some of these drug adverse effects. Pharmacogenomics aims to understand the relationship between genetic factors and inter-individual variations in drug responses, and to translate this information in therapy tailored to individual patient genetics. Relatively few efforts have been made to investigate the role of pharmacogenetics in the individual response to anti-PD drugs. Thus, many genetic variations and polymorphisms in myriad of different proteins can influence individual response to anti-PD drugs.

Genetic variation associated with cardiovascular risk in autoimmune diseases

PubMed Central

Perrotti, Pedro P.; Aterido, Adrià; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Gutiérrez, Benjamín; Gomollón, Fernando; García-Planella, Esther; Fernández, Emilia; Sanmartí, Raimon; Gratacós, Jordi; Martínez-Taboada, Víctor Manuel; Rodríguez-Rodríguez, Luís; Palau, Núria; Tortosa, Raül; Corbeto, Mireia L.; Lasanta, María L.; Marsal, Sara; Julià, Antonio

2017-01-01

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity. PMID:28982122

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

PubMed Central

Acland, Gregory M.

2014-01-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision. PMID:22065099

Genome-wide genetic investigation of serological measures of common infections

PubMed Central

Rubicz, Rohina; Yolken, Robert; Drigalenko, Eugene; Carless, Melanie A; Dyer, Thomas D; Kent Jr, Jack; Curran, Joanne E; Johnson, Matthew P; Cole, Shelley A; Fowler, Sharon P; Arya, Rector; Puppala, Sobha; Almasy, Laura; Moses, Eric K; Kraig, Ellen; Duggirala, Ravindranath; Blangero, John; Leach, Charles T; Göring, Harald HH

2015-01-01

Populations and individuals differ in susceptibility to infections because of a number of factors, including host genetic variation. We previously demonstrated that differences in antibody titer, which reflect infection history, are significantly heritable. Here we attempt to identify the genetic factors influencing variation in these serological phenotypes. Blood samples from >1300 Mexican Americans were quantified for IgG antibody level against 12 common infections, selected on the basis of their reported role in cardiovascular disease risk: Chlamydia pneumoniae; Helicobacter pylori; Toxoplasma gondii; cytomegalovirus; herpes simplex I virus; herpes simplex II virus; human herpesvirus 6 (HHV6); human herpesvirus 8 (HHV8); varicella zoster virus; hepatitis A virus (HAV); influenza A virus; and influenza B virus. Pathogen-specific quantitative antibody levels were analyzed, as were three measures of pathogen burden. Genome-wide linkage and joint linkage and association analyses were performed using ~1 million SNPs. Significant linkage (lod scores >3.0) was obtained for HHV6 (on chromosome 7), HHV8 (on chromosome 6), and HAV (on chromosome 13). SNP rs4812712 on chromosome 20 was significantly associated with C. pneumoniae (P=5.3 × 10−8). However, no genome-wide significant loci were obtained for the other investigated antibodies. We conclude that it is possible to localize host genetic factors influencing some of these antibody traits, but that further larger-scale investigations will be required to elucidate the genetic mechanisms contributing to variation in antibody levels. PMID:25758998

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies.

PubMed

Miyadera, Keiko; Acland, Gregory M; Aguirre, Gustavo D

2012-02-01

Considerable clinical and molecular variations have been known in retinal blinding diseases in man and also in dogs. Different forms of retinal diseases occur in specific breed(s) caused by mutations segregating within each isolated breeding population. While molecular studies to find genes and mutations underlying retinal diseases in dogs have benefited largely from the phenotypic and genetic uniformity within a breed, within- and across-breed variations have often played a key role in elucidating the molecular basis. The increasing knowledge of phenotypic, allelic, and genetic heterogeneities in canine retinal degeneration has shown that the overall picture is rather more complicated than initially thought. Over the past 20 years, various approaches have been developed and tested to search for genes and mutations underlying genetic traits in dogs, depending on the availability of genetic tools and sample resources. Candidate gene, linkage analysis, and genome-wide association studies have so far identified 24 mutations in 18 genes underlying retinal diseases in at least 58 dog breeds. Many of these genes have been associated with retinal diseases in humans, thus providing opportunities to study the role in pathogenesis and in normal vision. Application in therapeutic interventions such as gene therapy has proven successful initially in a naturally occurring dog model followed by trials in human patients. Other genes whose human homologs have not been associated with retinal diseases are potential candidates to explain equivalent human diseases and contribute to the understanding of their function in vision.

The current state of play on the molecular genetics of depression.

PubMed

Cohen-Woods, S; Craig, I W; McGuffin, P

2013-04-01

It has been well established that both genes and non-shared environment contribute substantially to the underlying aetiology of major depressive disorder (MDD). A comprehensive overview of genetic research in MDD is presented. Method Papers were retrieved from PubMed up to December 2011, using many keywords including: depression, major depressive disorder, genetics, rare variants, gene-environment, whole genome, epigenetics, and specific candidate genes and variants. These were combined in a variety of permutations. Linkage studies have yielded some promising chromosomal regions in MDD. However, there is a continued lack of consistency in association studies, in both candidate gene and genome-wide association studies (GWAS). Numerous factors may account for variable results including the use of different diagnostic approaches, small samples in early studies, population stratification, epigenetic phenomena, copy number variation (CNV), rare variation, and phenotypic and allelic heterogeneity. The conflicting results are also probably, in part, a consequence of environmental factors not being considered or controlled for. Each research group has to identify what issues their sample may best address. We suggest that, where possible, more emphasis should be placed on the environment in molecular behavioural genetics to identify individuals at environmental high risk in addition to genetic high risk. Sequencing should be used to identify rare and alternative variation that may act as a risk factor, and a systems biology approach including gene-gene interactions and pathway analyses would be advantageous. GWAS may require even larger samples with reliably defined (sub)phenotypes.

Heterozygosity-fitness correlations among wild populations of European tree frog (Hyla arborea) detect fixation load.

PubMed

Luquet, E; David, P; Lena, J-P; Joly, P; Konecny, L; Dufresnes, C; Perrin, N; Plenet, S

2011-05-01

Quantifying the impacts of inbreeding and genetic drift on fitness traits in fragmented populations is becoming a major goal in conservation biology. Such impacts occur at different levels and involve different sets of loci. Genetic drift randomly fixes slightly deleterious alleles leading to different fixation load among populations. By contrast, inbreeding depression arises from highly deleterious alleles in segregation within a population and creates variation among individuals. A popular approach is to measure correlations between molecular variation and phenotypic performances. This approach has been mainly used at the individual level to detect inbreeding depression within populations and sometimes at the population level but without consideration about the genetic processes measured. For the first time, we used in this study a molecular approach considering both the interpopulation and intrapopulation level to discriminate the relative importance of inbreeding depression vs. fixation load in isolated and non-fragmented populations of European tree frog (Hyla arborea), complemented with interpopulational crosses. We demonstrated that the positive correlations observed between genetic heterozygosity and larval performances on merged data were mainly caused by co-variations in genetic diversity and fixation load among populations rather than by inbreeding depression and segregating deleterious alleles within populations. Such a method is highly relevant in a conservation perspective because, depending on how populations lose fitness (inbreeding vs. fixation load), specific management actions may be designed to improve the persistence of populations. © 2011 Blackwell Publishing Ltd.

Contrasting support for alternative models of genomic variation based on microhabitat preference: species-specific effects of climate change in alpine sedges.

PubMed

Massatti, Rob; Knowles, L Lacey

2016-08-01

Deterministic processes may uniquely affect codistributed species' phylogeographic patterns such that discordant genetic variation among taxa is predicted. Yet, explicitly testing expectations of genomic discordance in a statistical framework remains challenging. Here, we construct spatially and temporally dynamic models to investigate the hypothesized effect of microhabitat preferences on the permeability of glaciated regions to gene flow in two closely related montane species. Utilizing environmental niche models from the Last Glacial Maximum and the present to inform demographic models of changes in habitat suitability over time, we evaluate the relative probabilities of two alternative models using approximate Bayesian computation (ABC) in which glaciated regions are either (i) permeable or (ii) a barrier to gene flow. Results based on the fit of the empirical data to data sets simulated using a spatially explicit coalescent under alternative models indicate that genomic data are consistent with predictions about the hypothesized role of microhabitat in generating discordant patterns of genetic variation among the taxa. Specifically, a model in which glaciated areas acted as a barrier was much more probable based on patterns of genomic variation in Carex nova, a wet-adapted species. However, in the dry-adapted Carex chalciolepis, the permeable model was more probable, although the difference in the support of the models was small. This work highlights how statistical inferences can be used to distinguish deterministic processes that are expected to result in discordant genomic patterns among species, including species-specific responses to climate change. © 2016 John Wiley & Sons Ltd.

Demographic loss, genetic structure and the conservation implications for Indian tigers.

PubMed

Mondol, Samrat; Bruford, Michael W; Ramakrishnan, Uma

2013-07-07

India is home to approximately 60 per cent of the world's remaining wild tigers, a species that has declined in the last few centuries to occupy less than 7 per cent of its former geographical range. While Indian tiger numbers have somewhat stabilized in recent years, they remain low and populations are highly fragmented. Therefore, the application of evidence-based demographic and genetic management to enhance the remaining populations is a priority. In this context, and using genetic data from historical and modern tigers, we investigated anthropogenic impacts on genetic variation in Indian tigers using mitochondrial and nuclear genetic markers. We found a very high number of historical mitochondrial DNA variants, 93 per cent of which are not detected in modern populations. Population differentiation was higher in modern tigers. Simulations incorporating historical data support population decline, and suggest high population structure in extant populations. Decreased connectivity and habitat loss as a result of ongoing fragmentation in the Indian subcontinent has therefore resulted in a loss of genetic variants and increased genetic differentiation among tiger populations. These results highlight that anthropogenic fragmentation and species-specific demographic processes can interact to alter the partitioning of genetic variation over very short time scales. We conclude that ongoing strategies to maximize the size of some tiger populations, at the expense of losing others, is an inadequate conservation strategy, as it could result in a loss of genetic diversity that may be of adaptive significance for this emblematic species.

Demographic loss, genetic structure and the conservation implications for Indian tigers

PubMed Central

Mondol, Samrat; Bruford, Michael W.; Ramakrishnan, Uma

2013-01-01

India is home to approximately 60 per cent of the world's remaining wild tigers, a species that has declined in the last few centuries to occupy less than 7 per cent of its former geographical range. While Indian tiger numbers have somewhat stabilized in recent years, they remain low and populations are highly fragmented. Therefore, the application of evidence-based demographic and genetic management to enhance the remaining populations is a priority. In this context, and using genetic data from historical and modern tigers, we investigated anthropogenic impacts on genetic variation in Indian tigers using mitochondrial and nuclear genetic markers. We found a very high number of historical mitochondrial DNA variants, 93 per cent of which are not detected in modern populations. Population differentiation was higher in modern tigers. Simulations incorporating historical data support population decline, and suggest high population structure in extant populations. Decreased connectivity and habitat loss as a result of ongoing fragmentation in the Indian subcontinent has therefore resulted in a loss of genetic variants and increased genetic differentiation among tiger populations. These results highlight that anthropogenic fragmentation and species-specific demographic processes can interact to alter the partitioning of genetic variation over very short time scales. We conclude that ongoing strategies to maximize the size of some tiger populations, at the expense of losing others, is an inadequate conservation strategy, as it could result in a loss of genetic diversity that may be of adaptive significance for this emblematic species. PMID:23677341

MECP2 variation in Rett syndrome-An overview of current coverage of genetic and phenotype data within existing databases.

PubMed

Townend, Gillian S; Ehrhart, Friederike; van Kranen, Henk J; Wilkinson, Mark; Jacobsen, Annika; Roos, Marco; Willighagen, Egon L; van Enckevort, David; Evelo, Chris T; Curfs, Leopold M G

2018-04-27

Rett syndrome (RTT) is a monogenic rare disorder that causes severe neurological problems. In most cases, it results from a loss-of-function mutation in the gene encoding methyl-CPG-binding protein 2 (MECP2). Currently, about 900 unique MECP2 variations (benign and pathogenic) have been identified and it is suspected that the different mutations contribute to different levels of disease severity. For researchers and clinicians, it is important that genotype-phenotype information is available to identify disease-causing mutations for diagnosis, to aid in clinical management of the disorder, and to provide counseling for parents. In this study, 13 genotype-phenotype databases were surveyed for their general functionality and availability of RTT-specific MECP2 variation data. For each database, we investigated findability and interoperability alongside practical user functionality, and type and amount of genetic and phenotype data. The main conclusions are that, as well as being challenging to find these databases and specific MECP2 variants held within, interoperability is as yet poorly developed and requires effort to search across databases. Nevertheless, we found several thousand online database entries for MECP2 variations and their associated phenotypes, diagnosis, or predicted variant effects, which is a good starting point for researchers and clinicians who want to provide, annotate, and use the data. © 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.

Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail

PubMed Central

Seppälä, Otto; Langeloh, Laura

2016-01-01

Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals’ genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals’ genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Maes, Hermine H; Sundquist, Kristina; Lichtenstein, Paul; Sundquist, Jan

2015-04-01

Prior studies, utilizing interview-based assessments, suggest that most of the genetic risk factors for drug abuse (DA) are non-specific with a minority acting specifically on risk for abuse of particular psychoactive substance classes. We seek to replicate these findings using objective national registry data. We examined abuse of cannabis, stimulants (including cocaine) and sedatives ascertained from national Swedish registers in male-male monozygotic (1720 pairs) and dizygotic twins (1219 pairs) combined with near-age full siblings (76,457 pairs) to provide sufficient power. Modeling was performed using Mx. A common pathway model fitted better than an independent pathway model. The latent liability to DA was highly heritable but also influenced by shared environment. Cannabis, stimulant and sedative abuse all loaded strongly on the common factor. Estimates for the total heritability for the three forms of substance abuse ranged from 64 to 70%. Between 75 and 90% of that genetic risk was non-specific, coming from the common factor with the remainder deriving from substance specific genetic risk factors. By contrast, all of the shared environmental effects, which accounted for 18-20% of the variance in liability, were non-specific. In accord with prior studies based on personal interviews, the large preponderance of genetic risk factors for abuse of specific classes of psychoactive substance are non-specific. These results suggest that genetic variation in the primary sites of action of the psychoactive drugs, which differ widely across most drug classes, play a minor role in human individual differences in risk for DA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pharmacogenomics in pediatric rheumatology.

PubMed

Becker, Mara L

2012-09-01

Despite major advancements in therapeutics, variability in drug response remains a challenge in both adults and children diagnosed with rheumatic disease. The genetic contribution to interindividual variability has emerged as a promising avenue of exploration; however, challenges remain in making this knowledge relevant in the clinical realm. New genetic associations in patients with rheumatic disease have been reported for disease modifying antirheumatic drugs, antimetabolites and biologic drugs. However, many of these findings are in need of replication, and few have taken into account the concept of ontogeny, specific to pediatrics. In the current era in which we practice, genetic variation will undoubtedly contribute to variability in therapeutic response and may be a factor that will ultimately impact individualized care. However, preliminary studies have shown that there are many hurdles that need to be overcome as we explore pharmacogenomic associations specifically in the field of pediatric rheumatology.

Genetic variation in tree structure and its relation to size in Douglas-fir: I. Biomass partitioning, foliage efficiency, stem form, and wood density.

Treesearch

J.B. St. Clair

1994-01-01

Genetic variation and covariation among traits of tree size and structure were assessed in an 18-year-old Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) genetic test in the Coast Range of Oregon. Considerable genetic variation was found in size, biomass partitioning, and wood density, and genetic gains may be...

Population genetic analysis and bioclimatic modeling in Agave striata in the Chihuahuan Desert indicate higher genetic variation and lower differentiation in drier and more variable environments.

PubMed

Trejo, Laura; Alvarado-Cárdenas, Leonardo O; Scheinvar, Enrique; Eguiarte, Luis E

2016-06-01

Is there an association between bioclimatic variables and genetic variation within species? This question can be approached by a detailed analysis of population genetics parameters along environmental gradients in recently originated species (so genetic drift does not further obscure the patterns). The genus Agave, with more than 200 recent species encompassing a diversity of morphologies and distributional patterns, is an adequate system for such analyses. We studied Agave striata, a widely distributed species from the Chihuahuan Desert, with a distinctive iteroparous reproductive ecology and two recognized subspecies with clear morphological differences. We used population genetic analyses along with bioclimatic studies to understand the effect of environment on the genetic variation and differentiation of this species. We analyzed six populations of the subspecies A. striata subsp. striata, with a southern distribution, and six populations of A. striata subsp. falcata, with a northern distribution, using 48 ISSR loci and a total of 541 individuals (averaging 45 individuals per population). We assessed correlations between population genetics parameters (the levels of genetic variation and differentiation) and the bioclimatic variables of each population. We modeled each subspecies distribution and used linear correlations and multifactorial analysis of variance. Genetic variation (measured as expected heterozygosity) increased at higher latitudes. Higher levels of genetic variation in populations were associated with a higher variation in environmental temperature and lower precipitation. Stronger population differentiation was associated with wetter and more variable precipitation in the southern distribution of the species. The two subspecies have genetic differences, which coincide with their climatic differences and potential distributions. Differences in genetic variation among populations and the genetic differentiation between A. striata subsp. striata and A. striata subsp. falcata is correlated with differences in environmental climatic variables along their distribution. We found two distinct gene pools that suggest active differentiation and perhaps incipient speciation. The detected association between genetic variation and environment variables indicates that climatic variables are playing an important role in the differentiation of A. striata. © 2016 Botanical Society of America.

The potential of shifting recombination hotspots to increase genetic gain in livestock breeding.

PubMed

Gonen, Serap; Battagin, Mara; Johnston, Susan E; Gorjanc, Gregor; Hickey, John M

2017-07-04

This study uses simulation to explore and quantify the potential effect of shifting recombination hotspots on genetic gain in livestock breeding programs. We simulated three scenarios that differed in the locations of quantitative trait nucleotides (QTN) and recombination hotspots in the genome. In scenario 1, QTN were randomly distributed along the chromosomes and recombination was restricted to occur within specific genomic regions (i.e. recombination hotspots). In the other two scenarios, both QTN and recombination hotspots were located in specific regions, but differed in whether the QTN occurred outside of (scenario 2) or inside (scenario 3) recombination hotspots. We split each chromosome into 250, 500 or 1000 regions per chromosome of which 10% were recombination hotspots and/or contained QTN. The breeding program was run for 21 generations of selection, after which recombination hotspot regions were kept the same or were shifted to adjacent regions for a further 80 generations of selection. We evaluated the effect of shifting recombination hotspots on genetic gain, genetic variance and genic variance. Our results show that shifting recombination hotspots reduced the decline of genetic and genic variance by releasing standing allelic variation in the form of new allele combinations. This in turn resulted in larger increases in genetic gain. However, the benefit of shifting recombination hotspots for increased genetic gain was only observed when QTN were initially outside recombination hotspots. If QTN were initially inside recombination hotspots then shifting them decreased genetic gain. Shifting recombination hotspots to regions of the genome where recombination had not occurred for 21 generations of selection (i.e. recombination deserts) released more of the standing allelic variation available in each generation and thus increased genetic gain. However, whether and how much increase in genetic gain was achieved by shifting recombination hotspots depended on the distribution of QTN in the genome, the number of recombination hotspots and whether QTN were initially inside or outside recombination hotspots. Our findings show future scope for targeted modification of recombination hotspots e.g. through changes in zinc-finger motifs of the PRDM9 protein to increase genetic gain in production species.

The role of invertases in plant compensatory responses to simulated herbivory

USDA-ARS?s Scientific Manuscript database

The ability of a plant to recover from mammalian herbivory by exhibiting enhanced growth and reproduction compared to unharmed plants, is called compensation. Although it is clear that genetic variation for compensation exists, little is known about the specific genes underpinnings leading this fitn...

Evolution and genetic diversity of Theileria.

PubMed

Sivakumar, Thillaiampalam; Hayashida, Kyoko; Sugimoto, Chihiro; Yokoyama, Naoaki

2014-10-01

Theileria parasites infect a wide range of domestic and wild ruminants worldwide, causing diseases with varying degrees of severity. A broad classification, based on the parasite's ability to transform the leukocytes of host animals, divides Theileria into two groups, consisting of transforming and non-transforming species. The evolution of transforming Theileria has been accompanied by drastic changes in its genetic makeup, such as acquisition or expansion of gene families, which are thought to play critical roles in the transformation of host cells. Genetic variation among Theileria parasites is sometimes linked with host specificity and virulence in the parasites. Immunity against Theileria parasites primarily involves cell-mediated immune responses in the host. Immunodominance and major histocompatibility complex class I phenotype-specificity result in a host immunity that is tightly focused and strain-specific. Immune escape in Theileria is facilitated by genetic diversity in its antigenic determinants, which potentially results in a loss of T cell receptor recognition in its host. In the recent past, several reviews have focused on genetic diversity in the transforming species, Theileriaparva and Theileriaannulata. In contrast, genetic diversity in Theileriaorientalis, a benign non-transforming parasite, which occasionally causes disease outbreaks in cattle, has not been extensively examined. In this review, therefore, we provide an outline of the evolution of Theileria, which includes T. orientalis, and discuss the possible mechanisms generating genetic diversity among parasite populations. Additionally, we discuss the potential implications of a genetically diverse parasite population in the context of Theileria vaccine development. Copyright © 2014 Elsevier B.V. All rights reserved.

Temporal genetic structure in a poecilogonous polychaete: the interplay of developmental mode and environmental stochasticity

PubMed Central

2014-01-01

Background Temporal variation in the genetic structure of populations can be caused by multiple factors, including natural selection, stochastic environmental variation, migration, or genetic drift. In benthic marine species, the developmental mode of larvae may indicate a possibility for temporal genetic variation: species with dispersive planktonic larvae are expected to be more likely to show temporal genetic variation than species with benthic or brooded non-dispersive larvae, due to differences in larval mortality and dispersal ability. We examined temporal genetic structure in populations of Pygospio elegans, a poecilogonous polychaete with within-species variation in developmental mode. P. elegans produces either planktonic, benthic, or intermediate larvae, varying both among and within populations, providing a within-species test of the generality of a relationship between temporal genetic variation and larval developmental mode. Results In contrast to our expectations, our microsatellite analyses of P. elegans revealed temporal genetic stability in the UK population with planktonic larvae, whereas there was variation indicative of drift in temporal samples of the populations from the Baltic Sea, which have predominantly benthic and intermediate larvae. We also detected temporal variation in relatedness within these populations. A large temporal shift in genetic structure was detected in a population from the Netherlands, having multiple developmental modes. This shift could have been caused by local extiction due to extreme environmental conditions and (re)colonization by planktonic larvae from neighboring populations. Conclusions In our study of P. elegans, temporal genetic variation appears to be due to not only larval developmental mode, but also the stochastic environment of adults. Large temporal genetic shifts may be more likely in marine intertidal habitats (e.g. North Sea and Wadden Sea) which are more prone to environmental stochasticity than the sub-tidal Baltic habitats. Sub-tidal and/or brackish (less saline) habitats may support smaller P. elegans populations and these may be more susceptible to the effects of random genetic drift. Moreover, higher frequencies of asexual reproduction and the benthic larval developmental mode in these populations leads to higher relatedness and contributes to drift. Our results indicate that a general relationship between larval developmental mode and temporal genetic variation may not exist. PMID:24447386

Temporal genetic structure in a poecilogonous polychaete: the interplay of developmental mode and environmental stochasticity.

PubMed

Kesäniemi, Jenni E; Mustonen, Marina; Boström, Christoffer; Hansen, Benni W; Knott, K Emily

2014-01-22

Temporal variation in the genetic structure of populations can be caused by multiple factors, including natural selection, stochastic environmental variation, migration, or genetic drift. In benthic marine species, the developmental mode of larvae may indicate a possibility for temporal genetic variation: species with dispersive planktonic larvae are expected to be more likely to show temporal genetic variation than species with benthic or brooded non-dispersive larvae, due to differences in larval mortality and dispersal ability. We examined temporal genetic structure in populations of Pygospio elegans, a poecilogonous polychaete with within-species variation in developmental mode. P. elegans produces either planktonic, benthic, or intermediate larvae, varying both among and within populations, providing a within-species test of the generality of a relationship between temporal genetic variation and larval developmental mode. In contrast to our expectations, our microsatellite analyses of P. elegans revealed temporal genetic stability in the UK population with planktonic larvae, whereas there was variation indicative of drift in temporal samples of the populations from the Baltic Sea, which have predominantly benthic and intermediate larvae. We also detected temporal variation in relatedness within these populations. A large temporal shift in genetic structure was detected in a population from the Netherlands, having multiple developmental modes. This shift could have been caused by local extiction due to extreme environmental conditions and (re)colonization by planktonic larvae from neighboring populations. In our study of P. elegans, temporal genetic variation appears to be due to not only larval developmental mode, but also the stochastic environment of adults. Large temporal genetic shifts may be more likely in marine intertidal habitats (e.g. North Sea and Wadden Sea) which are more prone to environmental stochasticity than the sub-tidal Baltic habitats. Sub-tidal and/or brackish (less saline) habitats may support smaller P. elegans populations and these may be more susceptible to the effects of random genetic drift. Moreover, higher frequencies of asexual reproduction and the benthic larval developmental mode in these populations leads to higher relatedness and contributes to drift. Our results indicate that a general relationship between larval developmental mode and temporal genetic variation may not exist.

Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.

PubMed

Sirugo, Giorgio; Hennig, Branwen J; Adeyemo, Adebowale A; Matimba, Alice; Newport, Melanie J; Ibrahim, Muntaser E; Ryckman, Kelli K; Tacconelli, Alessandra; Mariani-Costantini, Renato; Novelli, Giuseppe; Soodyall, Himla; Rotimi, Charles N; Ramesar, Raj S; Tishkoff, Sarah A; Williams, Scott M

2008-07-01

Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease.

Why genes don't count (for racial differences in health).

PubMed Central

Goodman, A H

2000-01-01

There is a paradoxical relationship between "race" and genetics. Whereas genetic data were first used to prove the validity of race, since the early 1970s they have been used to illustrate the invalidity of biological races. Indeed, race does not account for human genetic variation, which is continuous, complexly structured, constantly changing, and predominantly within "races." Despite the disproof of race-as-biology, genetic variation continues to be used to explain racial differences. Such explanations require the acceptance of 2 disproved assumptions: that genetic variation explains variation in disease and that genetic variation explains racial variation in disease. While the former is a form of geneticization, the notion that genes are the primary determinants of biology and behavior, the latter represents a form of racialization, an exaggeration of the salience of race. Using race as a proxy for genetic differences limits understandings of the complex interactions among political-economic processes, lived experiences, and human biologies. By moving beyond studies of racialized genetics, we can clarify the processes by which varied and interwoven forms of racialization and racism affect individuals "under the skin." PMID:11076233

Why genes don't count (for racial differences in health).

PubMed

Goodman, A H

2000-11-01

There is a paradoxical relationship between "race" and genetics. Whereas genetic data were first used to prove the validity of race, since the early 1970s they have been used to illustrate the invalidity of biological races. Indeed, race does not account for human genetic variation, which is continuous, complexly structured, constantly changing, and predominantly within "races." Despite the disproof of race-as-biology, genetic variation continues to be used to explain racial differences. Such explanations require the acceptance of 2 disproved assumptions: that genetic variation explains variation in disease and that genetic variation explains racial variation in disease. While the former is a form of geneticization, the notion that genes are the primary determinants of biology and behavior, the latter represents a form of racialization, an exaggeration of the salience of race. Using race as a proxy for genetic differences limits understandings of the complex interactions among political-economic processes, lived experiences, and human biologies. By moving beyond studies of racialized genetics, we can clarify the processes by which varied and interwoven forms of racialization and racism affect individuals "under the skin."

Convergence between biological, behavioural and genetic determinants of obesity.

PubMed

Ghosh, Sujoy; Bouchard, Claude

2017-12-01

Multiple biological, behavioural and genetic determinants or correlates of obesity have been identified to date. Genome-wide association studies (GWAS) have contributed to the identification of more than 100 obesity-associated genetic variants, but their roles in causal processes leading to obesity remain largely unknown. Most variants are likely to have tissue-specific regulatory roles through joint contributions to biological pathways and networks, through changes in gene expression that influence quantitative traits, or through the regulation of the epigenome. The recent availability of large-scale functional genomics resources provides an opportunity to re-examine obesity GWAS data to begin elucidating the function of genetic variants. Interrogation of knockout mouse phenotype resources provides a further avenue to test for evidence of convergence between genetic variation and biological or behavioural determinants of obesity.

TnSeq of Mycobacterium tuberculosis clinical isolates reveals strain-specific antibiotic liabilities

PubMed Central

Carey, Allison F.; Rock, Jeremy M.; Krieger, Inna V.; Gagneux, Sebastien; Sacchettini, James C.; Fortune, Sarah M.

2018-01-01

Once considered a phenotypically monomorphic bacterium, there is a growing body of work demonstrating heterogeneity among Mycobacterium tuberculosis (Mtb) strains in clinically relevant characteristics, including virulence and response to antibiotics. However, the genetic and molecular basis for most phenotypic differences among Mtb strains remains unknown. To investigate the basis of strain variation in Mtb, we performed genome-wide transposon mutagenesis coupled with next-generation sequencing (TnSeq) for a panel of Mtb clinical isolates and the reference strain H37Rv to compare genetic requirements for in vitro growth across these strains. We developed an analytic approach to identify quantitative differences in genetic requirements between these genetically diverse strains, which vary in genomic structure and gene content. Using this methodology, we found differences between strains in their requirements for genes involved in fundamental cellular processes, including redox homeostasis and central carbon metabolism. Among the genes with differential requirements were katG, which encodes the activator of the first-line antitubercular agent isoniazid, and glcB, which encodes malate synthase, the target of a novel small-molecule inhibitor. Differences among strains in their requirement for katG and glcB predicted differences in their response to these antimicrobial agents. Importantly, these strain-specific differences in antibiotic response could not be predicted by genetic variants identified through whole genome sequencing or by gene expression analysis. Our results provide novel insight into the basis of variation among Mtb strains and demonstrate that TnSeq is a scalable method to predict clinically important phenotypic differences among Mtb strains. PMID:29505613

Conservation implications of the genetic diversity of Gymnospermium microrrhynchum in Korea.

PubMed

Lee, S H; Yeon, M H; Shim, J K

2016-10-24

Gymnospermium microrrhynchum (Berberidaceae) is an ephemeral perennial herb with a limited distributional range in the Baekdudaegan mountain areas of the Korean Peninsula, and is designated a rare plant by the Korean Forest Service. Information about its genetic variation and structure is important for developing successful conservation strategies. To investigate the genetic variation within and among seven G. microrrhynchum populations, random amplified polymorphic DNA data were obtained for 207 individuals. The populations exhibited relatively low genetic diversity: the percentage of polymorphic bands (PPB) ranged from 32.1 to 66.7% (mean = 51.4%) and Nei's gene diversity (H E ) ranged from 0.116 to 0.248 (mean = 0.188). However, genetic diversity at the species level was relatively high (PPB = 98.7%, H E = 0.349). An analysis of molecular variance revealed high differentiation among populations (Φ ST = 0.6818), but the low gene flow value (N m = 0.117) suggests a low level of gene exchange occurs among populations. Principal coordinates analysis revealed that individuals were separated according to population. The high level of genetic differentiation and restricted gene flow among G. microrrhynchum populations, which resulted from their isolation in alpine areas after the Ice Age, indicates that it is essential to protect and manage all populations, rather than focus on specific populations, in order to maintain the genetic diversity of this species.

The contribution of additive genetic variation to personality variation: heritability of personality.

PubMed

Dochtermann, Ned A; Schwab, Tori; Sih, Andrew

2015-01-07

Individual animals frequently exhibit repeatable differences from other members of their population, differences now commonly referred to as 'animal personality'. Personality differences can arise, for example, from differences in permanent environmental effects--including parental and epigenetic contributors--and the effect of additive genetic variation. Although several studies have evaluated the heritability of behaviour, less is known about general patterns of heritability and additive genetic variation in animal personality. As overall variation in behaviour includes both the among-individual differences that reflect different personalities and temporary environmental effects, it is possible for personality to be largely genetically influenced even when heritability of behaviour per se is quite low. The relative contribution of additive genetic variation to personality variation can be estimated whenever both repeatability and heritability are estimated for the same data. Using published estimates to address this issue, we found that approximately 52% of animal personality variation was attributable to additive genetic variation. Thus, while the heritability of behaviour is often moderate or low, the heritability of personality is much higher. Our results therefore (i) demonstrate that genetic differences are likely to be a major contributor to variation in animal personality and (ii) support the phenotypic gambit: that evolutionary inferences drawn from repeatability estimates may often be justified. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Prioritization based on neutral genetic diversity may fail to conserve important characteristics in cattle breeds.

PubMed

Hall, S J G; Lenstra, J A; Deeming, D C

2012-06-01

Conservation of the intraspecific genetic diversity of livestock species requires protocols that assess between-breed genetic variability and also take into account differences among individuals within breeds. Here, we focus on variation between breeds. Conservation of neutral genetic variation has been seen as promoting, through linkage processes, the retention of useful and potentially useful variation. Using public information on beef cattle breeds, with a total of 165 data sets each relating to a breed comparison of a performance variable, we have tested this paradigm by calculating the correlations between pairwise breed differences in performance and pairwise genetic distances deduced from biochemical and immunological polymorphisms, microsatellites and single-nucleotide polymorphisms. As already observed in floral and faunal biodiversity, significant positive correlations (n=54) were found, but many correlations were non-significant (n=100) or significantly negative (n=11). This implies that maximizing conserved neutral genetic variation with current techniques may conserve breed-level genetic variation in some traits but not in others and supports the view that genetic distance measurements based on neutral genetic variation are not sufficient as a determinant of conservation priority among breeds. © 2011 Blackwell Verlag GmbH.

Genetic variation in CD38 and breastfeeding experience interact to impact infants’ attention to social eye cues

PubMed Central

Krol, Kathleen M.; Monakhov, Mikhail; Lai, Poh San; Ebstein, Richard P.; Grossmann, Tobias

2015-01-01

Attending to emotional information conveyed by the eyes is an important social skill in humans. The current study examined this skill in early development by measuring attention to eyes while viewing emotional faces in 7-mo-old infants. In particular, we investigated individual differences in infant attention to eyes in the context of genetic variation (CD38 rs3796863 polymorphism) and experiential variation (exclusive breastfeeding duration) related to the oxytocin system. Our results revealed that, whereas infants at this age show a robust fear bias (increased attention to fearful eyes), their attention to angry and happy eyes varies as a function of exclusive breastfeeding experience and genetic variation in CD38. Specifically, extended exclusive breastfeeding duration selectively enhanced looking preference to happy eyes and decreased looking to angry eyes. Importantly, however, this interaction was impacted by CD38 variation, such that only the looking preferences of infants homozygous for the C allele of rs3796863 were affected by breastfeeding experience. This genotype has been associated with reduced release of oxytocin and higher rates of autism. In contrast, infants with the CA/AA genotype showed similar looking preferences regardless of breastfeeding exposure. Thus, differences in the sensitivity to emotional eyes may be linked to an interaction between the endogenous (CD38) and exogenous (breastfeeding) availability of oxytocin. These findings underline the importance of maternal care and the oxytocin system in contributing to the early development of responding to social eye cues. PMID:26371313

Variation in Airway Responsiveness of Male C57BL/6 Mice from 5 Vendors

PubMed Central

Chang, Herng-Yu Sucie; Mitzner, Wayne; Watson, Julie

2012-01-01

Mice are now the most commonly used animal model for the study of asthma. The mouse asthma model has many characteristics of the human pathology, including allergic sensitization and airway hyperresponsiveness. Inbred strains are commonly used to avoid variations due to genetic background, but variations due to rearing environment are not as well recognized. After a change in mouse vendors and a switch from C57BL/6J mice to C57BL/6N mice, we noted significant differences in airway responsiveness between the substrains. To further investigate the effect of vendor, we tested C57BL/6N mice from 3 other vendors and found significant differences between several of the substrains. To test whether this difference was due to genetic drift or rearing environment, we purchased new groups of mice from all 5 vendors, bred them in separate vendor-specific groups under uniform environmental conditions, and tested male first generation (F1) offspring at 8 to 10 wk of age. These F1 mice showed no significant differences in airway responsiveness, indicating that the rearing environment rather than genetic differences was responsible for the initial variation in pulmonary phenotype. The environmental factors that caused the phenotypic variation are unknown. However, differences between vendor in feed components, bedding type, or microbiome could have contributed. Whatever the basis, investigators using mouse models of asthma should be cautious in comparing data from mice obtained from different vendors. PMID:23043804

Variation in MHC class II B genes in marbled murrelets: implications for delineating conservation units

Treesearch

C. Vásquez-Carrillo; V. Friesen; L. Hall; M.Z. Peery

2013-01-01

Conserving genetic variation is critical for maintaining the evolutionary potential and viability of a species. Genetic studies seeking to delineate conservation units, however, typically focus on characterizing neutral genetic variation and may not identify populations harboring local adaptations. Here, variation at two major histocompatibility complex (MHC) class II...

Evolutionary Determinants of Genetic Variation in Susceptibility to Infectious Diseases in Humans

PubMed Central

Baker, Christi; Antonovics, Janis

2012-01-01

Although genetic variation among humans in their susceptibility to infectious diseases has long been appreciated, little focus has been devoted to identifying patterns in levels of variation in susceptibility to different diseases. Levels of genetic variation in susceptibility associated with 40 human infectious diseases were assessed by a survey of studies on both pedigree-based quantitative variation, as well as studies on different classes of marker alleles. These estimates were correlated with pathogen traits, epidemiological characteristics, and effectiveness of the human immune response. The strongest predictors of levels of genetic variation in susceptibility were disease characteristics negatively associated with immune effectiveness. High levels of genetic variation were associated with diseases with long infectious periods and for which vaccine development attempts have been unsuccessful. These findings are consistent with predictions based on theoretical models incorporating fitness costs associated with the different types of resistance mechanisms. An appreciation of these observed patterns will be a valuable tool in directing future research given that genetic variation in disease susceptibility has large implications for vaccine development and epidemiology. PMID:22242158

Beyond Punnett Squares: Student Word Association and Explanations of Phenotypic Variation through an Integrative Quantitative Genetics Unit Investigating Anthocyanin Inheritance and Expression in "Brassica rapa" Fast Plants

ERIC Educational Resources Information Center

Batzli, Janet M.; Smith, Amber R.; Williams, Paul H.; McGee, Seth A.; Dosa, Katalin; Pfammatter, Jesse

2014-01-01

Genetics instruction in introductory biology is often confined to Mendelian genetics and avoids the complexities of variation in quantitative traits. Given the driving question "What determines variation in phenotype (Pv)? (Pv=Genotypic variation Gv + environmental variation Ev)," we developed a 4-wk unit for an inquiry-based laboratory…

Variation of genetic diversity in a rapidly expanding population of the greater long-tailed hamster (Tscherskia triton) as revealed by microsatellites.

PubMed

Xu, Laixiang; Xue, Huiliang; Song, Mingjing; Zhao, Qinghua; Dong, Jingping; Liu, Juan; Guo, Yu; Xu, Tongqin; Cao, Xiaoping; Wang, Fusheng; Wang, Shuqing; Hao, Shushen; Yang, Hefang; Zhang, Zhibin

2013-01-01

Genetic diversity is essential for persistence of animal populations over both the short- and long-term. Previous studies suggest that genetic diversity may decrease with population decline due to genetic drift or inbreeding of small populations. For oscillating populations, there are some studies on the relationship between population density and genetic diversity, but these studies were based on short-term observation or in low-density phases. Evidence from rapidly expanding populations is lacking. In this study, genetic diversity of a rapidly expanding population of the Greater long-tailed hamsters during 1984-1990, in the Raoyang County of the North China Plain was studied using DNA microsatellite markers. Results show that genetic diversity was positively correlated with population density (as measured by % trap success), and the increase in population density was correlated with a decrease of genetic differentiation between the sub-population A and B. The genetic diversity tended to be higher in spring than in autumn. Variation in population density and genetic diversity are consistent between sub-population A and B. Such results suggest that dispersal is density- and season-dependent in a rapidly expanding population of the Greater long-tailed hamster. For typically solitary species, increasing population density can increase intra-specific attack, which is a driving force for dispersal. This situation is counterbalanced by decreasing population density caused by genetic drift or inbreeding as the result of small population size. Season is a major factor influencing population density and genetic diversity. Meanwhile, roads, used to be considered as geographical isolation, have less effect on genetic differentiation in a rapidly expanding population. Evidences suggest that gene flow (Nm) is positively correlated with population density, and it is significant higher in spring than that in autumn.

The devil is in the details: genetic variation in introduced populations and its contributions to invasion.

PubMed

Dlugosch, Katrina M; Anderson, Samantha R; Braasch, Joseph; Cang, F Alice; Gillette, Heather D

2015-05-01

The influence of genetic variation on invasion success has captivated researchers since the start of the field of invasion genetics 50 years ago. We review the history of work on this question and conclude that genetic variation-as surveyed with molecular markers-appears to shape invasion rarely. Instead, there is a significant disconnect between marker assays and ecologically relevant genetic variation in introductions. We argue that the potential for adaptation to facilitate invasion will be shaped by the details of genotypes affecting phenotypes, and we highlight three areas in which we see opportunities to make powerful new insights. (i) The genetic architecture of adaptive variation. Traits shaped by large-effect alleles may be strongly impacted by founder events yet more likely to respond to selection when genetic drift is strong. Large-effect loci may be especially relevant for traits involved in biotic interactions. (ii) Cryptic genetic variation exposed during invasion. Introductions have strong potential to uncover masked variation due to alterations in genetic and ecological environments. (iii) Genetic interactions during admixture of multiple source populations. As divergence among sources increases, positive followed by increasingly negative effects of admixture should be expected. Although generally hypothesized to be beneficial during invasion, admixture is most often reported among sources of intermediate divergence, supporting the possibility that incompatibilities among divergent source populations might be limiting their introgression. Finally, we note that these details of invasion genetics can be coupled with comparative demographic analyses to link genetic changes to the evolution of invasiveness itself. © 2015 John Wiley & Sons Ltd.

Genetic and environmental influences on Anxious/Depression during childhood: a study from the Netherlands Twin Register.

PubMed

Boomsma, D I; van Beijsterveldt, C E M; Hudziak, J J

2005-11-01

For a large sample of twin pairs from the Netherlands Twins Register who were recruited at birth and followed through childhood, we obtained parental ratings of Anxious/Depression (A/D). Maternal ratings were obtained at ages 3 years (for 9025 twin pairs), 5 years (9222 pairs), 7 years (7331 pairs), 10 years (4430 pairs) and 12 years (2363 pairs). For 60-90% of the pairs, father ratings were also available. Multivariate genetic models were used to test for rater-independent and rater-specific assessments of A/D and to determine the genetic and environmental influences on individual differences in A/D at different ages. At all ages, monozygotic twins resembled each other more closely for A/D than dizygotic twins, implying genetic influences on variation in A/D. Opposite sex twin pairs resembled each other to same extent as same-sex dizygotic twins, suggesting that the same genes are expressed in boys and girls. Heritability estimates for rater-independent A/D were high in 3-year olds (76%) and decreased in size as children grew up [60% at age 5, 67% at age 7, 53% at age 10 (60% in boys) and 48% at age 12 years]. The decrease in genetic influences was accompanied by an increase in the influence of the shared family environment [absent at ages 3 and 7, 16% at age 5, 20% at age 10 (5% in boys) and 18% at age 12 years]. The agreement between parental A/D ratings was between 0.5 and 0.7, with somewhat higher correlations for the youngest group. Disagreement in ratings between the parents was not merely the result of unreliability or rater bias. Both the parents provided unique information from their own perspective on the behavior of their children. Significant influences of genetic and shared environmental factors were found for the unique parental views. At all ages, the contribution of shared environmental factors to variation in rater-specific views was higher for father ratings. Also, at all ages except age 12, the heritability estimates for the rater-specific phenotype were higher for mother ratings (59% at age 3 and decreasing to 27% at age 12 years) than for father ratings (between 14 and 29%). Differences between children, even as young as 3 years, in A/D are to a large extent due to genetic differences. As children grow up, the variation in A/D is due in equal parts to genetic and environmental influences. Anxious/Depression, unlike many other common childhood psychopathologies, is influenced by the shared family environment. These findings may provide support for why certain family therapeutic approaches are effective in the A/D spectrum of illnesses.

Genetic variation of apolipoproteins, diet and other environmental interactions; an updated review.

PubMed

Sotos-Prieto, Mercedes; Peñalvo, José Luis

2013-01-01

This paper summarizes the recent findings from studies investigating the potential environmental modulation of the genetic variation of apolipoprotein genes on metabolic traits. We reviewed nutrigenetic studies evaluating variations on apolipoproteins-related genes and its associated response to nutrients (mostly dietary fatty acids) or any other dietary or environmental component. Most revised research studied single nucleotide polymorphism (SNP) and specific nutrients through small intervention studies, and only few interactions have been replicated in large and independent populations (as in the case of -265T > C SNP in APOA2 gene). Although current knowledge shows that variations on apolipoprotein genes may contribute to the different response on metabolic traits due to dietary interventions, evidence is still scarce and results are inconsistent. Success in this area will require going beyond the limitations of current experimental designs and explore the hypotheses within large populations. Some of these limitations are being covered by the rapidly advance in high-throughput technologies and large scale-genome wide association studies. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

The genealogy and genetic viability of reintroduced Yellowstone grey wolves.

PubMed

Vonholdt, Bridgett M; Stahler, Daniel R; Smith, Douglas W; Earl, Dent A; Pollinger, John P; Wayne, Robert K

2008-01-01

The recovery of the grey wolf in Yellowstone National Park is an outstanding example of a successful reintroduction. A general question concerning reintroduction is the degree to which genetic variation has been preserved and the specific behavioural mechanisms that enhance the preservation of genetic diversity and reduce inbreeding. We have analysed 200 Yellowstone wolves, including all 31 founders, for variation in 26 microsatellite loci over the 10-year reintroduction period (1995-2004). The population maintained high levels of variation (1995 H(0) = 0.69; 2004 H(0) = 0.73) with low levels of inbreeding (1995 F(IS) = -0.063; 2004 F(IS) = -0.051) and throughout, the population expanded rapidly (N(1995) = 21; N(2004) = 169). Pedigree-based effective population size ratios did not vary appreciably over the duration of population expansion (1995 N(e)/N(g) = 0.29; 2000 N(e)/N(g) = 0.26; 2004 N(e)/N(g) = 0.33). We estimated kinship and found only two of 30 natural breeding pairs showed evidence of being related (average r = -0.026, SE = 0.03). We reconstructed the genealogy of 200 wolves based on genetic and field data and discovered that they avoid inbreeding through a wide variety of behavioural mechanisms including absolute avoidance of breeding with related pack members, male-biased dispersal to packs where they breed with nonrelatives, and female-biased subordinate breeding. We documented a greater diversity of such population assembly patterns in Yellowstone than previously observed in any other natural wolf population. Inbreeding avoidance is nearly absolute despite the high probability of within-pack inbreeding opportunities and extensive interpack kinship ties between adjacent packs. Simulations showed that the Yellowstone population has levels of genetic variation similar to that of a population managed for high variation and low inbreeding, and greater than that expected for random breeding within packs or across the entire breeding pool. Although short-term losses in variation seem minimal, future projections of the population at carrying capacity suggest significant inbreeding depression will occur without connectivity and migratory exchange with other populations.

Demography of Genotypes: Failure of the Limited Life-Span Paradigm in Drosophila melanogaster

NASA Astrophysics Data System (ADS)

Curtsinger, James W.; Fukui, Hidenori H.; Townsend, David R.; Vaupel, James W.

1992-10-01

Experimental systems that are amenable to genetic manipulation can be used to address fundamental questions about genetic and nongenetic determinants of longevity. Analysis of large cohorts of ten genotypes of Drosophila melanogaster raised under conditions that favored extended survival has revealed variation between genotypes in both the slope and location of age-specific mortality curves. More detailed examination of a single genotype showed that the mortality trajectory was best fit by a two-stage Gompertz model, with no age-specific increase in mortality rates beyond 30 days after emergence. These results are contrary to the limited life-span paradigm, which postulates well-defined, genotype-specific limits on life-span and brief periods of intense and rapidly accelerating mortality rates at the oldest ages.

Differential influences of local subpopulations on regional diversity and differentiation for greater sage-grouse (Centrocercus urophasianus)

USGS Publications Warehouse

Row, Jeffery R.; Oyler-McCance, Sara J.; Fedy, Brad C.

2016-01-01

The distribution of spatial genetic variation across a region can shape evolutionary dynamics and impact population persistence. Local population dynamics and among-population dispersal rates are strong drivers of this spatial genetic variation, yet for many species we lack a clear understanding of how these population processes interact in space to shape within-species genetic variation. Here, we used extensive genetic and demographic data from 10 subpopulations of greater sage-grouse to parameterize a simulated approximate Bayesian computation (ABC) model and (i) test for regional differences in population density and dispersal rates for greater sage-grouse subpopulations in Wyoming, and (ii) quantify how these differences impact subpopulation regional influence on genetic variation. We found a close match between observed and simulated data under our parameterized model and strong variation in density and dispersal rates across Wyoming. Sensitivity analyses suggested that changes in dispersal (via landscape resistance) had a greater influence on regional differentiation, whereas changes in density had a greater influence on mean diversity across all subpopulations. Local subpopulations, however, varied in their regional influence on genetic variation. Decreases in the size and dispersal rates of central populations with low overall and net immigration (i.e. population sources) had the greatest negative impact on genetic variation. Overall, our results provide insight into the interactions among demography, dispersal and genetic variation and highlight the potential of ABC to disentangle the complexity of regional population dynamics and project the genetic impact of changing conditions.

Plant defense phenotypes determine the consequences of volatile emission for individuals and neighbors

PubMed Central

Schuman, Meredith C; Allmann, Silke; Baldwin, Ian T

2015-01-01

Plants are at the trophic base of terrestrial ecosystems, and the diversity of plant species in an ecosystem is a principle determinant of community structure. This may arise from diverse functional traits among species. In fact, genetic diversity within species can have similarly large effects. However, studies of intraspecific genetic diversity have used genotypes varying in several complex traits, obscuring the specific phenotypic variation responsible for community-level effects. Using lines of the wild tobacco Nicotiana attenuata genetically altered in specific well-characterized defense traits and planted into experimental populations in their native habitat, we investigated community-level effects of trait diversity in populations of otherwise isogenic plants. We conclude that the frequency of defense traits in a population can determine the outcomes of these traits for individuals. Furthermore, our results suggest that some ecosystem-level services afforded by genetically diverse plant populations could be recaptured in intensive monocultures engineered to be functionally diverse. DOI: http://dx.doi.org/10.7554/eLife.04490.001 PMID:25873033

The Influence of Major Life Events on Economic Attitudes in a World of Gene-Environment Interplay.

PubMed

Hatemi, Peter K

2013-10-01

The role of "genes" on political attitudes has gained attention across disciplines. However, person-specific experiences have yet to be incorporated into models that consider genetic influences. Relying on a gene-environment interplay approach, this study explicates how life-events, such as losing one's job or suffering a financial loss, influence economic policy attitudes. The results indicate genetic and environmental variance on support for unions, immigration, capitalism, socialism and property tax is moderated by financial risks. Changes in the magnitude of genetic influences, however, are temporary. After two years, the phenotypic effects of the life events remain on most attitudes, but changes in the sources of individual differences do not. Univariate twin models that estimate the independent contributions of genes and environment on the variation of attitudes appear to provide robust baseline indicators of sources of individual differences. These estimates, however, are not event or day specific. In this way, genetic influences add stability, while environment cues change, and this process is continually updated.

Genetic exchange in an arbuscular mycorrhizal fungus results in increased rice growth and altered mycorrhiza-specific gene transcription.

PubMed

Colard, Alexandre; Angelard, Caroline; Sanders, Ian R

2011-09-01

Arbuscular mycorrhizal fungi (AMF) are obligate symbionts with most terrestrial plants. They improve plant nutrition, particularly phosphate acquisition, and thus are able to improve plant growth. In exchange, the fungi obtain photosynthetically fixed carbon. AMF are coenocytic, meaning that many nuclei coexist in a common cytoplasm. Genetic exchange recently has been demonstrated in the AMF Glomus intraradices, allowing nuclei of different Glomus intraradices strains to mix. Such genetic exchange was shown previously to have negative effects on plant growth and to alter fungal colonization. However, no attempt was made to detect whether genetic exchange in AMF can alter plant gene expression and if this effect was time dependent. Here, we show that genetic exchange in AMF also can be beneficial for rice growth, and that symbiosis-specific gene transcription is altered by genetic exchange. Moreover, our results show that genetic exchange can change the dynamics of the colonization of the fungus in the plant. Our results demonstrate that the simple manipulation of the genetics of AMF can have important consequences for their symbiotic effects on plants such as rice, which is considered the most important crop in the world. Exploiting natural AMF genetic variation by generating novel AMF genotypes through genetic exchange is a potentially useful tool in the development of AMF inocula that are more beneficial for crop growth.

Evolution and inheritance of early embryonic patterning in Drosophila simulans and D. sechellia.

PubMed

Lott, Susan E; Ludwig, Michael Z; Kreitman, Martin

2011-05-01

Pattern formation in Drosophila is a widely studied example of a robust developmental system. Such robust systems pose a challenge to adaptive evolution, as they mask variation that selection may otherwise act upon. Yet we find variation in the localization of expression domains (henceforth "stripe allometry") in the pattern formation pathway. Specifically, we characterize differences in the gap genes giant and Kruppel, and the pair-rule gene even-skipped, which differ between the sibling species Drosophila simulans and D. sechellia. In a double-backcross experiment, stripe allometry is consistent with maternal inheritance of stripe positioning and multiple genetic factors, with a distinct genetic basis from embryo length. Embryos produced by F1 and F2 backcross mothers exhibit novel spatial patterns of gene expression relative to the parental species, with no measurable increase in positional variance among individuals. Buffering of novel spatial patterns in the backcross genotypes suggests that robustness need not be disrupted in order for the trait to evolve, and perhaps the system is incapable of evolving to prevent the expression of all genetic variation. This limitation, and the ability of natural selection to act on minute genetic differences that are within the "margin of error" for the buffering mechanism, indicates that developmentally buffered traits can evolve without disruption of robustness. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.

PubMed

McMahon, George; Ring, Susan M; Davey-Smith, George; Timpson, Nicholas J

2015-10-15

Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. We carried out a case-control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E - 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. The majority of these associations were explained by the lead SNP rs9271768. Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy. © The Author 2015. Published by Oxford University Press.

RAPD-PCR and real-time PCR HRM based genetic variation evaluations of Urtica dioica parts, ecotypes and evaluations of morphotypes in Turkey.

PubMed

Uzonur, Irem; Akdeniz, Gamze; Katmer, Zeynep; Ersoy, Seyda Karaman

2013-01-01

Urtica dioica is an ethnobotanically and medicinally important Complementary and Alternative Medicine (CAM) plant worldwide and in Turkey; 90 % of herbal CAM applications depend on it in Turkey. It has a wide range of habitats in nearly all continents. It is found in all three phytogeographical regions in Turkey (Euro-Siberian, Irano-Turanian, Mediterranean) with high adaptivity to heterogeneous geographies such as climate, soil types and altitudes. This fact in relation to the assessment of chemical constituents of the plant and combining with further genetic and morphological variation data can assist and enhance the works for the utility and reliability of CAM applications in effect and activity of this plant species. In this work we have made some preliminary experiments with novel approaches to reveal the ecotypes and genetic variation of mighty ecotypes of Urtica dioica from different phytogeographical regions of Turkey (Euro-Siberian and Mediterranean). The ecotypes have heterogeneity in both its parts (leaf, stem, root) as revealed by Random Amplified Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR) using random primers and High-resolution Melt (HRM) analysis using Urtica dioica specific primers and universal chloroplast DNA (cpDNA) primers and morphological traits such as phenolic contents and antioxidant capacities of plants' leaf infusions as used in medicinal applications in Turkey. This work will contribute a lot for the development of molecular markers to detect the genetic variation and heterogeneity of Urtica dioica to further relate with expected phenotypes that are most useful and relevant in CAM applications.

Allozyme and RAPD Analysis of the Genetic Diversity and Geographic Variation in Wild Populations of the American Chestnut (Fagaceae)

Treesearch

Hongwen Huang; Fenny Dane; Thomas L. Kubisiak

1998-01-01

Genetic variation among 12 populations of the American chestnut (Custanea dentata) was investigated. Population genetic parameters estimated from allozyme variation suggest that C. dentata at both the population and species level has narrow genetic diversity as compared to other species in the genus. Average expected heterozygosity...

Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases

PubMed Central

Varela, Miguel A; Curtis, Helen J; Douglas, Andrew GL; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew JA

2016-01-01

Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets. PMID:25990798

Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases.

PubMed

Varela, Miguel A; Curtis, Helen J; Douglas, Andrew G L; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew J A

2016-02-01

Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets.

Variable sexually dimorphic gene expression in laboratory strains of Drosophila melanogaster.

PubMed

Baker, Dean A; Meadows, Lisa A; Wang, Jing; Dow, Julian At; Russell, Steven

2007-12-10

Wild-type laboratory strains of model organisms are typically kept in isolation for many years, with the action of genetic drift and selection on mutational variation causing lineages to diverge with time. Natural populations from which such strains are established, show that gender-specific interactions in particular drive many aspects of sequence level and transcriptional level variation. Here, our goal was to identify genes that display transcriptional variation between laboratory strains of Drosophila melanogaster, and to explore evidence of gender-biased interactions underlying that variability. Transcriptional variation among the laboratory genotypes studied occurs more frequently in males than in females. Qualitative differences are also apparent to suggest that genes within particular functional classes disproportionately display variation in gene expression. Our analysis indicates that genes with reproductive functions are most often divergent between genotypes in both sexes, however a large proportion of female variation can also be attributed to genes without expression in the ovaries. The present study clearly shows that transcriptional variation between common laboratory strains of Drosophila can differ dramatically due to sexual dimorphism. Much of this variation reflects sex-specific challenges associated with divergent physiological trade-offs, morphology and regulatory pathways operating within males and females.

Hemiclonal analysis of interacting phenotypes in male and female Drosophila melanogaster

PubMed Central

2014-01-01

Background Identifying the sources of variation in mating interactions between males and females is important because this variation influences the strength and/or the direction of sexual selection that populations experience. While the origins and effects of variation in male attractiveness and ornamentation have received much scrutiny, the causes and consequences of intraspecific variation in females have been relatively overlooked. We used cytogenetic cloning techniques developed for Drosophila melanogaster to create “hemiclonal” males and females with whom we directly observed sexual interaction between individuals of different known genetic backgrounds and measured subsequent reproductive outcomes. Using this approach, we were able to quantify the genetic contribution of each mate to the observed phenotypic variation in biologically important traits including mating speed, copulation duration, and subsequent offspring production, as well as measure the magnitude and direction of intersexual genetic correlation between female choosiness and male attractiveness. Results We found significant additive genetic variation contributing to mating speed that can be attributed to male genetic identity, female genetic identity, but not their interaction. Furthermore we found that phenotypic variation in copulation duration had a significant male-associated genetic component. Female genetic identity and the interaction between male and female genetic identity accounted for a substantial amount of the observed phenotypic variation in egg size. Although previous research predicts a trade-off between egg size and fecundity, this was not evident in our results. We found a strong negative genetic correlation between female choosiness and male attractiveness, a result that suggests a potentially important role for sexually antagonistic alleles in sexual selection processes in our population. Conclusion These results further our understanding of sexual selection because they identify that genetic identity plays a significant role in phenotypic variation in female behaviour and fecundity. This variation may be potentially due to ongoing sexual conflict found between the sexes for interacting phenotypes. Our unexpected observation of a negative correlation between female choosiness and male attractiveness highlights the need for more explicit theoretical models of genetic covariance to investigate the coevolution of female choosiness and male attractiveness. PMID:24884361

Heritability of seed weight in Maritime pine, a relevant trait in the transmission of environmental maternal effects

PubMed Central

Zas, R; Sampedro, L

2015-01-01

Quantitative seed provisioning is an important life-history trait with strong effects on offspring phenotype and fitness. As for any other trait, heritability estimates are vital for understanding its evolutionary dynamics. However, being a trait in between two generations, estimating additive genetic variation of seed provisioning requires complex quantitative genetic approaches for distinguishing between true genetic and environmental maternal effects. Here, using Maritime pine as a long-lived plant model, we quantified additive genetic variation of cone and seed weight (SW) mean and SW within-individual variation. We used a powerful approach combining both half-sib analysis and parent–offspring regression using several common garden tests established in contrasting environments to separate G, E and G × E effects. Both cone weight and SW mean showed significant genetic variation but were also influenced by the maternal environment. Most of the large variation in SW mean was attributable to additive genetic effects (h2=0.55–0.74). SW showed no apparent G × E interaction, particularly when accounting for cone weight covariation, suggesting that the maternal genotypes actively control the SW mean irrespective of the amount of resources allocated to cones. Within-individual variation in SW was low (12%) relative to between-individual variation (88%), and showed no genetic variation but was largely affected by the maternal environment, with greater variation in the less favourable sites for pine growth. In summary, results were very consistent between the parental and the offspring common garden tests, and clearly indicated heritable genetic variation for SW mean but not for within-individual variation in SW. PMID:25160045

Population-Specific Patterns of Linkage Disequilibrium and SNP Variation in Spring and Winter Polyploid Wheat

USDA-ARS?s Scientific Manuscript database

Single nucleotide polymorphisms (SNPs) are ideally suited for the construction of high-resolution genetic maps, studying population evolutionary history and performing genome-wide association mapping experiments. Here we used a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and po...

Additive genetic variation and evolvability of a multivariate trait can be increased by epistatic gene action.

PubMed

Griswold, Cortland K

2015-12-21

Epistatic gene action occurs when mutations or alleles interact to produce a phenotype. Theoretically and empirically it is of interest to know whether gene interactions can facilitate the evolution of diversity. In this paper, we explore how epistatic gene action affects the additive genetic component or heritable component of multivariate trait variation, as well as how epistatic gene action affects the evolvability of multivariate traits. The analysis involves a sexually reproducing and recombining population. Our results indicate that under stabilizing selection conditions a population with a mixed additive and epistatic genetic architecture can have greater multivariate additive genetic variation and evolvability than a population with a purely additive genetic architecture. That greater multivariate additive genetic variation can occur with epistasis is in contrast to previous theory that indicated univariate additive genetic variation is decreased with epistasis under stabilizing selection conditions. In a multivariate setting, epistasis leads to less relative covariance among individuals in their genotypic, as well as their breeding values, which facilitates the maintenance of additive genetic variation and increases a population׳s evolvability. Our analysis involves linking the combinatorial nature of epistatic genetic effects to the ancestral graph structure of a population to provide insight into the consequences of epistasis on multivariate trait variation and evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

RAPD analysis of genetic variation in the Australian fan flower, Scaevola.

PubMed

Swoboda, I; Bhalla, P L

1997-10-01

The use of randomly amplified polymorphic DNA (RAPD) to study genetic variability in Scaevola (family Goodeniaceae), a native Australian species used in ornamental horticulture, is demonstrated. Plants of the genus Scaevola are commonly known as "fan flowers," due to the fan-like shape of the flowers. Nineteen accessions of Scaevola (12 cultivated and 7 wild) were studied using 20 random decamer arbitrary primers. Eight primers gave a distinct reproducible amplification profile of 90 scorable polymorphic fragments, enabling the differentiation of the Scaevola accessions. RAPD amplification of genomic DNA revealed a high genetic variability among the different species of Scaevola studied. Molecular markers were used to calculate the similarity coefficients, which were then used for determining genetic distances between each of the accessions. Based on genetic distances, a dendrogram was constructed. Though the dendrogram is in general agreement with the taxonomy, it also highlights discrepancies in the classification. The RAPD data showed that Scaevola aemula (series Pogogynae) is closer to Scaevola glandulifera of series Globuliferae than to the rest of members of series Pogogynae. In addition, the RAPD banding pattern of white flower S. aemula, one of the commercial cultivars, was identical to that of Scaevola albida, indicating their genetic similarity. Our study showed that there is a large genetic distance between commercial cultivars of Scaevola (Purple Fanfare, Pink Perfection, and Mauve Cluster), indicating considerable genetic variation among them. The use of RAPDs in intra- and inter-specific breeding of Scaevola is also explored.

Genetic polymorphism of Malassezia furfur isolates from Han and Tibetan ethnic groups in China using DNA fingerprinting.

PubMed

Zhang, Hao; Zhang, Ruifeng; Ran, Yuping; Dai, Yaling; Lu, Yao; Wang, Peng

2010-12-01

Reported isolation rates of Malassezia yeast from human skin show geographic variations. In China, the populations of the Han (1,182.95 million) and Tibetan (5.41 million) ethnic groups are distributed over 9.6 and 3.27 million square kilometers respectively, making biodiversity research feasible and convenient. Malassezia furfur clinical strains (n = 29) isolated from different individuals, with or without associated dermatoses, of these two ethnic groups (15 Han and 12 Tibetan) were identified and analyzed with DNA fingerprinting using single primers specific to minisatellites. Using the Bionumerics software, we found that almost all M. furfur clinical isolates and type strains formed five distinct group clusters according to their associated skin diseases and the ethnic groups of the patients. These findings are the first to focus on the genetic diversity and relatedness of M. furfur in the Tibetan and Han ethnic groups in China and reveal genetic variation associated with related diseases, host ethnicity and geographic origin.

Progesterone Response Element Variation in the OXTR Promoter Region and Paternal Care in New World Monkeys.

PubMed

Vargas-Pinilla, Pedro; Babb, Paul; Nunes, Leandro; Paré, Pâmela; Rosa, Gabrielle; Felkl, Aline; Longo, Dânae; Salzano, Francisco M; Paixão-Côrtes, Vanessa R; Gonçalves, Gislene Lopes; Bortolini, Maria Cátira

2017-01-01

Paternal care is a complex social behavior common in primate species with socially monogamous mating systems and twin births. Evolutionary causes and consequences of such behavior are not well understood, nor are their neuroendocrine and genetic bases. However, the neuropeptide oxytocin (OXT) and its receptor (OXTR) are associated with parental care in mammalian lineages. Here we investigated the interspecific variation in the number of progesterone response elements (PREs) in the OXTR promoter region of 32 primate species, correlating genetic data with behavior, social systems, and ecological/life-history parameters, while controlling for phylogeny. We verified that PREs are only present in New World monkeys and that PRE number is significantly correlated with the presence of paternal care in this branch. We suggest that PRE number could be an essential part of the genetic repertoire that allowed the emergence of taxon-specific complex social behaviors, such as paternal care in marmosets and tamarins.

Complexity of genetic mechanisms conferring nonuniformity of recombination in maize.

PubMed

Pan, Qingchun; Deng, Min; Yan, Jianbing; Li, Lin

2017-04-26

Recombinations occur nonuniformly across the maize genome. To dissect the genetic mechanisms underlying the nonuniformity of recombination, we performed quantitative trait locus (QTL) mapping using recombinant inbred line populations. Genome-wide QTL scan identified hundreds of QTLs with both cis-prone and trans- effects for recombination number variation. To provide detailed insights into cis- factors associated with recombination variation, we examined the genomic features around recombination hot regions, including density of genes, DNA transposons, retrotransposons, and some specific motifs. Compared to recombination variation in whole genome, more QTLs were mapped for variations in recombination hot regions. The majority QTLs for recombination hot regions are trans-QTLs and co-localized with genes from the recombination pathway. We also found that recombination variation was positively associated with the presence of genes and DNA transposons, but negatively related to the presence of long terminal repeat retrotransposons. Additionally, 41 recombination hot regions were fine-mapped. The high-resolution genotyping of five randomly selected regions in two F 2 populations verified that they indeed have ultra-high recombination frequency, which is even higher than that of the well-known recombination hot regions sh1-bz and a1-sh2. Taken together, our results further our understanding of recombination variation in plants.

Fitness variation in response to artificial selection for reduced cell area, cell number and wing area in natural populations of Drosophila melanogaster.

PubMed

Trotta, Vincenzo; Calboli, Federico C F; Ziosi, Marcello; Cavicchi, Sandro

2007-08-16

Genetically based body size differences are naturally occurring in populations of Drosophila melanogaster, with bigger flies in the cold. Despite the cosmopolitan nature of body size clines in more than one Drosophila species, the actual selective mechanisms controlling the genetic basis of body size variation are not fully understood. In particular, it is not clear what the selective value of cell size and cell area variation exactly is. In the present work we determined variation in viability, developmental time and larval competitive ability in response to crowding at two temperatures after artificial selection for reduced cell area, cell number and wing area in four different natural populations of D. melanogaster. No correlated effect of selection on viability or developmental time was observed among all selected populations. An increase in competitive ability in one thermal environment (18 degrees C) under high larval crowding was observed as a correlated response to artificial selection for cell size. Viability and developmental time are not affected by selection for the cellular component of body size, suggesting that these traits only depend on the contingent genetic makeup of a population. The higher larval competitive ability shown by populations selected for reduced cell area seems to confirm the hypothesis that cell area mediated changes have a relationship with fitness, and might be the preferential way to change body size under specific circumstances.

Design of microarray experiments for genetical genomics studies.

PubMed

Bueno Filho, Júlio S S; Gilmour, Steven G; Rosa, Guilherme J M

2006-10-01

Microarray experiments have been used recently in genetical genomics studies, as an additional tool to understand the genetic mechanisms governing variation in complex traits, such as for estimating heritabilities of mRNA transcript abundances, for mapping expression quantitative trait loci, and for inferring regulatory networks controlling gene expression. Several articles on the design of microarray experiments discuss situations in which treatment effects are assumed fixed and without any structure. In the case of two-color microarray platforms, several authors have studied reference and circular designs. Here, we discuss the optimal design of microarray experiments whose goals refer to specific genetic questions. Some examples are used to illustrate the choice of a design for comparing fixed, structured treatments, such as genotypic groups. Experiments targeting single genes or chromosomic regions (such as with transgene research) or multiple epistatic loci (such as within a selective phenotyping context) are discussed. In addition, microarray experiments in which treatments refer to families or to subjects (within family structures or complex pedigrees) are presented. In these cases treatments are more appropriately considered to be random effects, with specific covariance structures, in which the genetic goals relate to the estimation of genetic variances and the heritability of transcriptional abundances.

Genetic correlation between autistic traits and IQ in a population-based sample of twins with autism spectrum disorders (ASDs).

PubMed

Nishiyama, Takeshi; Taniai, Hiroko; Taniai, Hitomi; Miyachi, Taishi; Ozaki, Koken; Tomita, Makoto; Sumi, Satoshi

2009-01-01

Although there is accumulating evidence that intelligence quotient (IQ) indexes some aspects of the autistic spectrum disorders (ASDs), the causal relationship between autistic traits and IQ remains controversial. We examined the sources of covariation between autistic traits and IQ. As males have a four times greater risk of ASDs than females, gender-specific effects were also explored. Autistic traits and IQ were assessed in 45 twin male-male, female-female and opposite-sex pairs ascertained by the regional screening system in Nagoya, Japan. Sex-limited Cholesky structural equation models were used to decompose the correlations between autistic traits and IQ into genetic and environmental components, including sex-specific factors. Genetic correlations between autistic traits and IQ were high and not significantly different between boys and girls (-0.94 and -0.95, respectively), but genetic factors underlying the autistic traits were not entirely shared with the IQ. The individual-specific environmental correlation between autistic traits and IQ was estimated at -0.29 for boys and -0.59 for girls. There is a substantial overlap between the genetic factors that influence individual variation in autistic traits and IQ, irrespective of gender. The individual life experiences that increase autistic traits, however, have a moderate overlap with those that contribute to individual IQs.

Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements

PubMed Central

Wang, Lu; Mariño-Ramírez, Leonardo

2017-01-01

Abstract Transposable element (TE) derived sequences are known to contribute to the regulation of the human genome. The majority of known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations. The extent to which human genetic variation caused by recent TE activity leads to regulatory polymorphisms among populations has yet to be thoroughly explored. In this study, we searched for associations between polymorphic TE (polyTE) loci and human gene expression levels using an expression quantitative trait loci (eQTL) approach. We compared locus-specific polyTE insertion genotypes to B cell gene expression levels among 445 individuals from 5 human populations. Numerous human polyTE loci correspond to both cis and trans eQTL, and their regulatory effects are directly related to cell type-specific function in the immune system. PolyTE loci are associated with differences in expression between European and African population groups, and a single polyTE loci is indirectly associated with the expression of numerous genes via the regulation of the B cell-specific transcription factor PAX5. The polyTE-gene expression associations we found indicate that human TE genetic variation can have important phenotypic consequences. Our results reveal that TE-eQTL are involved in population-specific gene regulation as well as transcriptional network modification. PMID:27998931

Examination of Association to Autism of Common Genetic Variation in Genes Related to Dopamine

PubMed Central

Anderson, B.M.; Schnetz-Boutaud, N.; Bartlett, J.; Wright, H.H.; Abramson, R.K.; Cuccaro, M.L.; Gilbert, J.R.; Pericak-Vance, M.A.; Haines, J.L.

2010-01-01

Autism is a severe neurodevelopmental disorder characterized by a triad of complications. Autistic individuals display significant disturbances in language and reciprocal social interactions, combined with repetitive and stereotypic behaviors. Prevalence studies suggest that autism is more common than originally believed, with recent estimates citing a rate of one in 150. Although this genomic approach has yielded multiple suggestive regions, a specific risk locus has yet to be identified and widely confirmed. Because many etiologies have been suggested for this complex syndrome, we hypothesize that one of the difficulties in identifying autism genes is that multiple genetic variants may be required to significantly increase the risk of developing autism. Thus we took the alternative approach of examining 14 prominent dopamine pathway candidate genes for detailed study by genotyping 28 SNPs. Although we did observe a nominally significant association for rs2239535 (p=.008) on chromosome 20, single locus analysis did not reveal any results as significant after correction for multiple comparisons. No significant interaction was identified when Multifactor Dimensionality Reduction (MDR) was employed to test specifically for multilocus effects. Although genome-wide linkage scans in autism have provided support for linkage to various loci along the dopamine pathway, our study does not provide strong evidence of linkage or association to any specific gene or combination of genes within the pathway. These results demonstrate that common genetic variation within the tested genes located within this pathway at most play a minor to moderate role in overall autism pathogenesis. PMID:19360691

A Genotypic-Oriented View of CFTR Genetics Highlights Specific Mutational Patterns Underlying Clinical Macrocategories of Cystic Fibrosis

PubMed Central

Lucarelli, Marco; Bruno, Sabina Maria; Pierandrei, Silvia; Ferraguti, Giampiero; Stamato, Antonella; Narzi, Fabiana; Amato, Annalisa; Cimino, Giuseppe; Bertasi, Serenella; Quattrucci, Serena; Strom, Roberto

2015-01-01

Cystic fibrosis (CF) is a monogenic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The genotype–phenotype relationship in this disease is still unclear, and diagnostic, prognostic and therapeutic challenges persist. We enrolled 610 patients with different forms of CF and studied them from a clinical, biochemical, microbiological and genetic point of view. Overall, there were 125 different mutated alleles (11 with novel mutations and 10 with complex mutations) and 225 genotypes. A strong correlation between mutational patterns at the genotypic level and phenotypic macrocategories emerged. This specificity appears to largely depend on rare and individual mutations, as well as on the varying prevalence of common alleles in different clinical macrocategories. However, 19 genotypes appeared to underlie different clinical forms of the disease. The dissection of the pathway from the CFTR mutated genotype to the clinical phenotype allowed to identify at least two components of the variability usually found in the genotype–phenotype relationship. One component seems to depend on the genetic variation of CFTR, the other component on the cumulative effect of variations in other genes and cellular pathways independent from CFTR. The experimental dissection of the overall biological CFTR pathway appears to be a powerful approach for a better comprehension of the genotype–phenotype relationship. However, a change from an allele-oriented to a genotypic-oriented view of CFTR genetics is mandatory, as well as a better assessment of sources of variability within the CFTR pathway. PMID:25910067

Assessing the potential for an ongoing arms race within and between the sexes: selection and heritable variation.

PubMed

Friberg, Urban; Lew, Timothy A; Byrne, Phillip G; Rice, William R

2005-07-01

In promiscuous species, sexual selection generates two opposing male traits: offense (acquiring new mates and supplanting stored sperm) and defense (enforcing fidelity on one's mates and preventing sperm displacement when this fails). Coevolution between these traits requires both additive genetic variation and associated natural selection. Previous work with Drosophila melanogaster found autosomal genetic variation for these traits among inbred lines from a mixture of populations, but only nonheritable genetic variation was found within a single outbred population. These results do not support ongoing antagonistic coevolution between offense and defense, nor between either of these male traits and female reproductive characters. Here we use a new method (hemiclonal analysis) to study genomewide genetic variation in a large outbred laboratory population of D. melanogaster. Hemiclonal analysis estimates the additive genetic variation among random, genomewide haplotypes taken from a large, outbred, locally adapted laboratory population and determines the direction of the selection gradient on this variation. In contrast to earlier studies, we found low but biologically significant heritable variation for defensive and offensive offspring production as well as all their components (P1, fidelity, P2, and remating). Genetic correlations between these traits were substantially different from those reported for inbred lines. A positive genetic correlation was found between defense and offense, demonstrating that some shared genes influence both traits. In addition to this common variation, evidence for unique genetic variation for each trait was also found, supporting an ongoing coevolutionary arms race between defense and offense. Reproductive conflict between males can strongly influence female fitness. Correspondingly, we found genetic variation in both defense and offense that affected female fitness. No evidence was found for intersexual conflict in the context of male defense, but we found substantial intersexual conflict in the context of male offensive sperm competitive ability. These results indicate that conflict between competing males also promotes an associated arms race between the sexes.

Evidence of weak genetic structure and recent gene flow between Bactrocera dorsalis s.s. and B. papayae, across Southern Thailand and West Malaysia, supporting a single target pest for SIT applications

PubMed Central

2014-01-01

Background Bactrocera dorsalis s.s. (Hendel) and B. papayae Drew & Hancock, are invasive pests belonging to the B. dorsalis complex. Their species status, based on morphology, is sometimes arguable. Consequently, the existence of cryptic species and/or population isolation may decrease the effectiveness of the sterile insect technique (SIT) due to an unknown degree of sexual isolation between released sterile flies and wild counterparts. To evaluate the genetic relationship and current demography in wild populations for guiding the application of area-wide integrated pest management using SIT, seven microsatellite-derived markers from B. dorsalis s.s. and another five from B. papayae were used for surveying intra- and inter-specific variation, population structure, and recent migration among sympatric and allopatric populations of the two morphological forms across Southern Thailand and West Malaysia. Results Basic genetic variations were not significantly different among forms, populations, and geographical areas (P > 0.05). Nonetheless, two sets of microsatellite markers showed significantly different levels of polymorphisms. Genetic differentiation between intra- and inter-specific differences was significant, but low. Seventeen populations revealed three hypothetical genetic clusters (K = 3) regardless of forms and geographical areas. The genetic structure of sympatric populations slightly changed during the different years of collection. Recent gene flow (m ≥ 0.10) was frequently detected whether samples were sympatric or allopatric. Ninety-five of 379 individuals distributed across the given area were designated as recent migrants or of admixed ancestry. As a consequence of substantial migration, no significant correlation between genetic and geographic distances was detected (R2 = 0.056, P = 0.650). Conclusions According to the 12 microsatellite variations, weak population structure and recent gene flow suggest that there is no status for cryptic species between B. dorsalis s.s. and B. papayae forms in Southern Thailand and West Malaysia. Both forms can be treated as a single target pest for the SIT program in an area-wide sense. Additionally, the result of species identification based on molecular data and morphological character are not congruent. The use of independent, multiple approaches in the characterization of the target population may ensure the effectiveness and feasibility of SIT-based control in the target area. PMID:24929425

Evidence of weak genetic structure and recent gene flow between Bactrocera dorsalis s.s. and B. papayae, across Southern Thailand and West Malaysia, supporting a single target pest for SIT applications.

PubMed

Aketarawong, Nidchaya; Isasawin, Siriwan; Thanaphum, Sujinda

2014-06-14

Bactrocera dorsalis s.s. (Hendel) and B. papayae Drew & Hancock, are invasive pests belonging to the B. dorsalis complex. Their species status, based on morphology, is sometimes arguable. Consequently, the existence of cryptic species and/or population isolation may decrease the effectiveness of the sterile insect technique (SIT) due to an unknown degree of sexual isolation between released sterile flies and wild counterparts. To evaluate the genetic relationship and current demography in wild populations for guiding the application of area-wide integrated pest management using SIT, seven microsatellite-derived markers from B. dorsalis s.s. and another five from B. papayae were used for surveying intra- and inter-specific variation, population structure, and recent migration among sympatric and allopatric populations of the two morphological forms across Southern Thailand and West Malaysia. Basic genetic variations were not significantly different among forms, populations, and geographical areas (P > 0.05). Nonetheless, two sets of microsatellite markers showed significantly different levels of polymorphisms. Genetic differentiation between intra- and inter-specific differences was significant, but low. Seventeen populations revealed three hypothetical genetic clusters (K = 3) regardless of forms and geographical areas. The genetic structure of sympatric populations slightly changed during the different years of collection. Recent gene flow (m ≥ 0.10) was frequently detected whether samples were sympatric or allopatric. Ninety-five of 379 individuals distributed across the given area were designated as recent migrants or of admixed ancestry. As a consequence of substantial migration, no significant correlation between genetic and geographic distances was detected (R2 = 0.056, P = 0.650). According to the 12 microsatellite variations, weak population structure and recent gene flow suggest that there is no status for cryptic species between B. dorsalis s.s. and B. papayae forms in Southern Thailand and West Malaysia. Both forms can be treated as a single target pest for the SIT program in an area-wide sense. Additionally, the result of species identification based on molecular data and morphological character are not congruent. The use of independent, multiple approaches in the characterization of the target population may ensure the effectiveness and feasibility of SIT-based control in the target area.

Compatibility of breeding for increased wood production and longterm sustainability: the genetic variation of seed orchard seed and associated risks.

Treesearch

R Johnson; S. Lipow

2002-01-01

Because breeding imposes strong artificial selection for a narrow suite of economically important traits, genetic variation is reduced in seedlings derived from operational seed orchards. Both quantitative genetics theory and studies of allozyme variation show that seed orchards contain most of the genetic diversity found in natural populations, although low-frequency...

Genetic variation in tree structure and its relation to size in Douglas-fir: II. crown form, branch characters, and foliage characters.

Treesearch

J.B. St. Clair

1994-01-01

Genetic variation and covariation among traits of tree size and structure were assessed in an 18-year-old Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) genetic test in the Coast Range of Oregon. Considerable genetic variation was found for relative crown width; stem increment per crown projection area; leaf...

Comparative epigenetic and genetic spatial structure of the perennial herb Helleborus foetidus: Isolation by environment, isolation by distance, and functional trait divergence.

PubMed

Herrera, Carlos M; Medrano, Mónica; Bazaga, Pilar

2017-08-16

Epigenetic variation can play a role in local adaptation; thus, there should be associations among epigenetic variation, environmental variation, and functional trait variation across populations. This study examines these relationships in the perennial herb Helleborus foetidus (Ranunculaceae). Plants from 10 subpopulations were characterized genetically (AFLP, SSR markers), epigenetically (MSAP markers), and phenotypically (20 functional traits). Habitats were characterized using six environmental variables. Isolation-by-distance (IBD) and isolation-by-environment (IBE) patterns of genetic and epigenetic divergence were assessed, as was the comparative explanatory value of geographical and environmental distance as predictors of epigenetic, genetic, and functional differentiation. Subpopulations were differentiated genetically, epigenetically, and phenotypically. Genetic differentiation was best explained by geographical distance, while epigenetic differentiation was best explained by environmental distance. Divergence in functional traits was correlated with environmental and epigenetic distances, but not with geographical and genetic distances. Results are compatible with the hypothesis that epigenetic IBE and functional divergence reflected responses to environmental variation. Spatial analyses simultaneously considering epigenetic, genetic, phenotypic and environmental information provide a useful tool to evaluate the role of environmental features as drivers of natural epigenetic variation between populations. © 2017 Botanical Society of America.

Genetic variation in South Indian castes: evidence from Y-chromosome, mitochondrial, and autosomal polymorphisms

PubMed Central

Watkins, WS; Thara, R; Mowry, BJ; Zhang, Y; Witherspoon, DJ; Tolpinrud, W; Bamshad, MJ; Tirupati, S; Padmavati, R; Smith, H; Nancarrow, D; Filippich, C; Jorde, LB

2008-01-01

Background Major population movements, social structure, and caste endogamy have influenced the genetic structure of Indian populations. An understanding of these influences is increasingly important as gene mapping and case-control studies are initiated in South Indian populations. Results We report new data on 155 individuals from four Tamil caste populations of South India and perform comparative analyses with caste populations from the neighboring state of Andhra Pradesh. Genetic differentiation among Tamil castes is low (RST = 0.96% for 45 autosomal short tandem repeat (STR) markers), reflecting a largely common origin. Nonetheless, caste- and continent-specific patterns are evident. For 32 lineage-defining Y-chromosome SNPs, Tamil castes show higher affinity to Europeans than to eastern Asians, and genetic distance estimates to the Europeans are ordered by caste rank. For 32 lineage-defining mitochondrial SNPs and hypervariable sequence (HVS) 1, Tamil castes have higher affinity to eastern Asians than to Europeans. For 45 autosomal STRs, upper and middle rank castes show higher affinity to Europeans than do lower rank castes from either Tamil Nadu or Andhra Pradesh. Local between-caste variation (Tamil Nadu RST = 0.96%, Andhra Pradesh RST = 0.77%) exceeds the estimate of variation between these geographically separated groups (RST = 0.12%). Low, but statistically significant, correlations between caste rank distance and genetic distance are demonstrated for Tamil castes using Y-chromosome, mtDNA, and autosomal data. Conclusion Genetic data from Y-chromosome, mtDNA, and autosomal STRs are in accord with historical accounts of northwest to southeast population movements in India. The influence of ancient and historical population movements and caste social structure can be detected and replicated in South Indian caste populations from two different geographic regions. PMID:19077280

Assessment of diversity among populations of Rauvolfia serpentina Benth. Ex. Kurtz. from Southern Western Ghats of India, based on chemical profiling, horticultural traits and RAPD analysis.

PubMed

Nair, Vadakkemuriyil Divya; Raj, Rajan Pillai Dinesh; Panneerselvam, Rajaram; Gopi, Ragupathi

2014-01-01

Genetic, morphological and chemical variations of ten natural populations of Rauvolfia serpentina Benth. Ex. Kurtz. from Southern Western Ghats of India were assessed using RAPD markers reserpine content and morphological traits. An estimate of genetic diversity and differentiation between genotypes of breeding germplasm is of key importance for its improvement. Populations were collected from different geographical regions. Data obtained through three different methods were compared and the correlation among them was estimated. Statistical analysis showed significant differences for all horticultural characteristics among the accessions suggesting that selection for relevant characteristics could be possible. Variation in the content of Reserpine ranges from 0.192 g/100 g (population from Tusharagiri) to 1.312 g/100 g (population from Aryankavu). A high diversity within population and high genetic differentiation among them based on RAPDs were revealed caused both by habitat fragmentation of the low size of most populations and the low level of gene flow among them. The UPGMA dendrogram and PCA analysis based on reserpine content yielded higher separation among populations indicated specific adaptation of populations into clusters each of them including populations closed to their geographical origin. Genetic, chemical and morphological data were correlated based on Mantel test. Given the high differentiation among populations conservation strategies should take into account genetic diversity and chemical variation levels in relation to bioclimatic and geographic location of populations. Our results also indicate that RAPD approach along with horticultural analysis seemed to be best suited for assessing with high accuracy the genetic relationships among distinct R. serpentina accessions. © 2013.

Gene expression divergence and nucleotide differentiation between males of different color morphs and mating strategies in the ruff

PubMed Central

Ekblom, Robert; Farrell, Lindsay L; Lank, David B; Burke, Terry

2012-01-01

By next generation transcriptome sequencing, it is possible to obtain data on both nucleotide sequence variation and gene expression. We have used this approach (RNA-Seq) to investigate the genetic basis for differences in plumage coloration and mating strategies in a non-model bird species, the ruff (Philomachus pugnax). Ruff males show enormous variation in the coloration of ornamental feathers, used for individual recognition. This polymorphism is linked to reproductive strategies, with dark males (Independents) defending territories on leks against other Independents, whereas white morphs (Satellites) co-occupy Independent's courts without agonistic interactions. Previous work found a strong genetic component for mating strategy, but the genes involved were not identified. We present feather transcriptome data of more than 6,000 de-novo sequenced ruff genes (although with limited coverage for many of them). None of the identified genes showed significant expression divergence between males, but many genetic markers showed nucleotide differentiation between different color morphs and mating strategies. These include several feather keratin genes, splicing factors, and the Xg blood-group gene. Many of the genes with significant genetic structure between mating strategies have not yet been annotated and their functions remain to be elucidated. We also conducted in-depth investigations of 28 pre-identified coloration candidate genes. Two of these (EDNRB and TYR) were specifically expressed in black- and rust-colored males, respectively. We have demonstrated the utility of next generation transcriptome sequencing for identifying and genotyping large number of genetic markers in a non-model species without previous genomic resources, and highlight the potential of this approach for addressing the genetic basis of ecologically important variation. PMID:23145334

Social-group identity and population substructure in admixed populations in New Mexico and Latin America.

PubMed

Healy, Meghan E; Hill, Deirdre; Berwick, Marianne; Edgar, Heather; Gross, Jessica; Hunley, Keith

2017-01-01

We examined the relationship between continental-level genetic ancestry and racial and ethnic identity in an admixed population in New Mexico with the goal of increasing our understanding of how racial and ethnic identity influence genetic substructure in admixed populations. Our sample consists of 98 New Mexicans who self-identified as Hispanic or Latino (NM-HL) and who further categorized themselves by race and ethnic subgroup membership. The genetic data consist of 270 newly-published autosomal microsatellites from the NM-HL sample and previously published data from 57 globally distributed populations, including 13 admixed samples from Central and South America. For these data, we 1) summarized the major axes of genetic variation using principal component analyses, 2) performed tests of Hardy Weinberg equilibrium, 3) compared empirical genetic ancestry distributions to those predicted under a model of admixture that lacked substructure, 4) tested the hypotheses that individuals in each sample had 100%, 0%, and the sample-mean percentage of African, European, and Native American ancestry. We found that most NM-HL identify themselves and their parents as belonging to one of two groups, conforming to a region-specific narrative that distinguishes recent immigrants from Mexico from individuals whose families have resided in New Mexico for generations and who emphasize their Spanish heritage. The "Spanish" group had significantly lower Native American ancestry and higher European ancestry than the "Mexican" group. Positive FIS values, PCA plots, and heterogeneous ancestry distributions suggest that most Central and South America admixed samples also contain substructure, and that this substructure may be related to variation in social identity. Genetic substructure appears to be common in admixed populations in the Americas and may confound attempts to identify disease-causing genes and to understand the social causes of variation in health outcomes and social inequality.

Comparative RNA sequencing reveals substantial genetic variation in endangered primates

PubMed Central

Perry, George H.; Melsted, Páll; Marioni, John C.; Wang, Ying; Bainer, Russell; Pickrell, Joseph K.; Michelini, Katelyn; Zehr, Sarah; Yoder, Anne D.; Stephens, Matthew; Pritchard, Jonathan K.; Gilad, Yoav

2012-01-01

Comparative genomic studies in primates have yielded important insights into the evolutionary forces that shape genetic diversity and revealed the likely genetic basis for certain species-specific adaptations. To date, however, these studies have focused on only a small number of species. For the majority of nonhuman primates, including some of the most critically endangered, genome-level data are not yet available. In this study, we have taken the first steps toward addressing this gap by sequencing RNA from the livers of multiple individuals from each of 16 mammalian species, including humans and 11 nonhuman primates. Of the nonhuman primate species, five are lemurs and two are lorisoids, for which little or no genomic data were previously available. To analyze these data, we developed a method for de novo assembly and alignment of orthologous gene sequences across species. We assembled an average of 5721 gene sequences per species and characterized diversity and divergence of both gene sequences and gene expression levels. We identified patterns of variation that are consistent with the action of positive or directional selection, including an 18-fold enrichment of peroxisomal genes among genes whose regulation likely evolved under directional selection in the ancestral primate lineage. Importantly, we found no relationship between genetic diversity and endangered status, with the two most endangered species in our study, the black and white ruffed lemur and the Coquerel's sifaka, having the highest genetic diversity among all primates. Our observations imply that many endangered lemur populations still harbor considerable genetic variation. Timely efforts to conserve these species alongside their habitats have, therefore, strong potential to achieve long-term success. PMID:22207615

The effects of child maltreatment on early signs of antisocial behavior: Genetic moderation by Tryptophan Hydroxylase, Serotonin Transporter, and Monoamine Oxidase-A-Genes

PubMed Central

Cicchetti, Dante; Rogosch, Fred A.; Thibodeau, Eric

2013-01-01

Gene-environment interaction effects in predicting antisocial behavior in late childhood were investigated among maltreated and nonmaltreated low-income children (N = 627, M age = 11.27). Variants in three genes, TPH1, 5-HTTLPR, and MAOA uVNTR, were examined. In addition to child maltreatment status, we also considered the impact of maltreatment subtypes, developmental timing of maltreatment, and chronicity. Indicators of antisocial behavior were obtained from self-, peer-, and adult counselor-reports. In a series of ANCOVAs, child maltreatment and its parameters demonstrated strong main effects on early antisocial behavior as assessed by all forms of report. Genetic effects operated primarily in the context of gene-environment interactions, moderating the impact of child maltreatment on outcomes. Across the three genes, among nonmaltreated children no differences in antisocial behavior were found based on genetic variation. In contrast, among maltreated children specific polymorphisms of TPH1, 5-HTTLPR, and MAOA were each related to heightened self-report of antisocial behavior; the interaction of 5-HTTLPR and developmental timing of maltreatment also indicated more severe antisocial outcomes for children with early onset and recurrent maltreatment based on genotype. TPH1 and 5-HTTLPR interacted with maltreatment subtype to predict peer-report of antisocial behavior; genetic variation contributed to larger differences in antisocial behavior among abused children. TPH1 and 5-HTTLPR polymorphisms also moderated the effects of maltreatment subtype on adult report of antisocial behavior; again genetic effects were strongest for children who were abused. Additionally, TPH1 moderated the effect of developmental timing of maltreatment and chronicity on adult report of antisocial behavior. The findings elucidate how genetic variation contributes to identifying which maltreated children are most vulnerable to antisocial development. PMID:22781862

Dissecting genetic architecture of startle response in Drosophila melanogaster using multi-omics information.

PubMed

Xue, Angli; Wang, Hongcheng; Zhu, Jun

2017-09-28

Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

Wide variation in virulence and genetic diversity of binucleate Rhizoctonia isolates associated with root rot of strawberry in Western Australia.

PubMed

Fang, Xiangling; Finnegan, Patrick M; Barbetti, Martin J

2013-01-01

Strawberry (Fragaria×ananassa) is one of the most important berry crops in the world. Root rot of strawberry caused by Rhizoctonia spp. is a serious threat to commercial strawberry production worldwide. However, there is no information on the genetic diversity and phylogenetic status of Rhizoctonia spp. associated with root rot of strawberry in Australia. To address this, a total of 96 Rhizoctonia spp. isolates recovered from diseased strawberry plants in Western Australia were characterized for their nuclear condition, virulence, genetic diversity and phylogenetic status. All the isolates were found to be binucleate Rhizoctonia (BNR). Sixty-five of the 96 BNR isolates were pathogenic on strawberry, but with wide variation in virulence, with 25 isolates having high virulence. Sequence analysis of the internal transcribed spacers of the ribosomal DNA separated the 65 pathogenic BNR isolates into six distinct clades. The sequence analysis also separated reference BNR isolates from strawberry or other crops across the world into clades that correspond to their respective anastomosis group (AG). Some of the pathogenic BNR isolates from this study were embedded in the clades for AG-A, AG-K and AG-I, while other isolates formed clades that were sister to the clades specific for AG-G, AG-B, AG-I and AG-C. There was no significant association between genetic diversity and virulence of these BNR isolates. This study demonstrates that pathogenic BNR isolates associated with root rot of strawberry in Western Australia have wide genetic diversity, and highlights new genetic groups not previously found to be associated with root rot of strawberry in the world (e.g., AG-B) or in Australia (e.g., AG-G). The wide variation in virulence and genetic diversity identified in this study will be of high value for strawberry breeding programs in selecting, developing and deploying new cultivars with resistance to these multi-genetic groups of BNR.

Aggregation of population‐based genetic variation over protein domain homologues and its potential use in genetic diagnostics

PubMed Central

Wiel, Laurens; Venselaar, Hanka; Veltman, Joris A.; Vriend, Gert

2017-01-01

Abstract Whole exomes of patients with a genetic disorder are nowadays routinely sequenced but interpretation of the identified genetic variants remains a major challenge. The increased availability of population‐based human genetic variation has given rise to measures of genetic tolerance that have been used, for example, to predict disease‐causing genes in neurodevelopmental disorders. Here, we investigated whether combining variant information from homologous protein domains can improve variant interpretation. For this purpose, we developed a framework that maps population variation and known pathogenic mutations onto 2,750 “meta‐domains.” These meta‐domains consist of 30,853 homologous Pfam protein domain instances that cover 36% of all human protein coding sequences. We find that genetic tolerance is consistent across protein domain homologues, and that patterns of genetic tolerance faithfully mimic patterns of evolutionary conservation. Furthermore, for a significant fraction (68%) of the meta‐domains high‐frequency population variation re‐occurs at the same positions across domain homologues more often than expected. In addition, we observe that the presence of pathogenic missense variants at an aligned homologous domain position is often paired with the absence of population variation and vice versa. The use of these meta‐domains can improve the interpretation of genetic variation. PMID:28815929

Distinctiveness of the Roma population within CYP2B6 worldwide variation.

PubMed

Tomas, Željka; Kuhanec, Antonija; Škarić-Jurić, Tatjana; Petranović, Matea Zajc; Narančić, Nina Smolej; Janićijević, Branka; Salihović, Marijana Peričić

2017-11-01

To determine variation of CYP2B6 gene within the genetically specific Croatian Roma (Gypsy) population originating from India and to examine it in the worldwide perspective. Seven SNP loci (rs12721655, rs2279343, rs28399499, rs34097093, rs3745274, rs7260329 and rs8192709) were genotyped in 439 subjects using Kompetitive Allele Specific PCR (KASP) method. The Croatian Roma took an outlying position in CYP2B6 variation from the worldwide perspective mainly due to their exceptionally high minor allele frequency (MAF) for rs8192709 (12.8%), and lower for rs2279343 (21.1%) compared with south Asian populations. This study provides the first data of several CYP2B6 polymorphisms in Roma population and indicates the need for systematic investigation of the most important pharmacogenes' variants in this large, transnationally isolated population worldwide.

Tissue-Specific Profiling Reveals Transcriptome Alterations in Arabidopsis Mutants Lacking Morphological Phenotypes[C][W

PubMed Central

Simon, Marissa; Bruex, Angela; Kainkaryam, Raghunandan M.; Zheng, Xiaohua; Huang, Ling; Woolf, Peter J.; Schiefelbein, John

2013-01-01

Traditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype. PMID:24014549

Age-specific infectious period shapes dynamics of pneumonia in bighorn sheep.

PubMed

Plowright, Raina K; Manlove, Kezia R; Besser, Thomas E; Páez, David J; Andrews, Kimberly R; Matthews, Patrick E; Waits, Lisette P; Hudson, Peter J; Cassirer, E Frances

2017-10-01

Superspreading, the phenomenon where a small proportion of individuals contribute disproportionately to new infections, has profound effects on disease dynamics. Superspreading can arise through variation in contacts, infectiousness or infectious periods. The latter has received little attention, yet it drives the dynamics of many diseases of critical public health, livestock health and conservation concern. Here, we present rare evidence of variation in infectious periods underlying a superspreading phenomenon in a free-ranging wildlife system. We detected persistent infections of Mycoplasma ovipneumoniae, the primary causative agent of pneumonia in bighorn sheep (Ovis canadensis), in a small number of older individuals that were homozygous at an immunologically relevant genetic locus. Interactions among age-structure, genetic composition and infectious periods may drive feedbacks in disease dynamics that determine the magnitude of population response to infection. Accordingly, variation in initial conditions may explain divergent population responses to infection that range from recovery to catastrophic decline and extirpation. © 2017 John Wiley & Sons Ltd/CNRS.

De novo assembly of soybean wild relatives for pan-genome analysis of diversity and agronomic traits.

PubMed

Li, Ying-hui; Zhou, Guangyu; Ma, Jianxin; Jiang, Wenkai; Jin, Long-guo; Zhang, Zhouhao; Guo, Yong; Zhang, Jinbo; Sui, Yi; Zheng, Liangtao; Zhang, Shan-shan; Zuo, Qiyang; Shi, Xue-hui; Li, Yan-fei; Zhang, Wan-ke; Hu, Yiyao; Kong, Guanyi; Hong, Hui-long; Tan, Bing; Song, Jian; Liu, Zhang-xiong; Wang, Yaoshen; Ruan, Hang; Yeung, Carol K L; Liu, Jian; Wang, Hailong; Zhang, Li-juan; Guan, Rong-xia; Wang, Ke-jing; Li, Wen-bin; Chen, Shou-yi; Chang, Ru-zhen; Jiang, Zhi; Jackson, Scott A; Li, Ruiqiang; Qiu, Li-juan

2014-10-01

Wild relatives of crops are an important source of genetic diversity for agriculture, but their gene repertoire remains largely unexplored. We report the establishment and analysis of a pan-genome of Glycine soja, the wild relative of cultivated soybean Glycine max, by sequencing and de novo assembly of seven phylogenetically and geographically representative accessions. Intergenomic comparisons identified lineage-specific genes and genes with copy number variation or large-effect mutations, some of which show evidence of positive selection and may contribute to variation of agronomic traits such as biotic resistance, seed composition, flowering and maturity time, organ size and final biomass. Approximately 80% of the pan-genome was present in all seven accessions (core), whereas the rest was dispensable and exhibited greater variation than the core genome, perhaps reflecting a role in adaptation to diverse environments. This work will facilitate the harnessing of untapped genetic diversity from wild soybean for enhancement of elite cultivars.

Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel.

PubMed

Mitt, Mario; Kals, Mart; Pärn, Kalle; Gabriel, Stacey B; Lander, Eric S; Palotie, Aarno; Ripatti, Samuli; Morris, Andrew P; Metspalu, Andres; Esko, Tõnu; Mägi, Reedik; Palta, Priit

2017-06-01

Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF)≥5% and low-frequency variants (0.5≤MAF<5%) across diverse populations, but the imputation of rare variation (MAF<0.5%) is still rather limited. In the current study, we evaluate imputation accuracy achieved with reference panels from diverse populations with a population-specific high-coverage (30 ×) whole-genome sequencing (WGS) based reference panel, comprising of 2244 Estonian individuals (0.25% of adult Estonians). Although the Estonian-specific panel contains fewer haplotypes and variants, the imputation confidence and accuracy of imputed low-frequency and rare variants was significantly higher. The results indicate the utility of population-specific reference panels for human genetic studies.

Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel

PubMed Central

Mitt, Mario; Kals, Mart; Pärn, Kalle; Gabriel, Stacey B; Lander, Eric S; Palotie, Aarno; Ripatti, Samuli; Morris, Andrew P; Metspalu, Andres; Esko, Tõnu; Mägi, Reedik; Palta, Priit

2017-01-01

Genetic imputation is a cost-efficient way to improve the power and resolution of genome-wide association (GWA) studies. Current publicly accessible imputation reference panels accurately predict genotypes for common variants with minor allele frequency (MAF)≥5% and low-frequency variants (0.5≤MAF<5%) across diverse populations, but the imputation of rare variation (MAF<0.5%) is still rather limited. In the current study, we evaluate imputation accuracy achieved with reference panels from diverse populations with a population-specific high-coverage (30 ×) whole-genome sequencing (WGS) based reference panel, comprising of 2244 Estonian individuals (0.25% of adult Estonians). Although the Estonian-specific panel contains fewer haplotypes and variants, the imputation confidence and accuracy of imputed low-frequency and rare variants was significantly higher. The results indicate the utility of population-specific reference panels for human genetic studies. PMID:28401899

Proteogenomic Investigation of Strain Variation in Clinical Mycobacterium tuberculosis Isolates.

PubMed

Heunis, Tiaan; Dippenaar, Anzaan; Warren, Robin M; van Helden, Paul D; van der Merwe, Ruben G; Gey van Pittius, Nicolaas C; Pain, Arnab; Sampson, Samantha L; Tabb, David L

2017-10-06

Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of the utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study, we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M. tuberculosis Latin American-Mediterranean isolates. Using this approach, we identified 59 peptides containing single amino acid variants, which covered ∼9% of all coding nonsynonymous single nucleotide variants detected by whole-genome sequencing. Furthermore, we identified 29 distinct peptides that mapped to a hypothetical protein not present in the M. tuberculosis H37Rv reference proteome. Here, we provide evidence for the expression of this protein in the clinical M. tuberculosis SAWC3651 isolate. The strain-specific databases enabled confirmation of genomic differences (i.e., large genomic regions of difference and nonsynonymous single nucleotide variants) in these two clinical M. tuberculosis isolates and allowed strain differentiation at the proteome level. Our results contribute to the growing field of clinical microbial proteogenomics and can improve our understanding of phenotypic variation in clinical M. tuberculosis isolates.

Toward a mtDNA locus-specific mutation database using the LOVD platform.

PubMed

Elson, Joanna L; Sweeney, Mary G; Procaccio, Vincent; Yarham, John W; Salas, Antonio; Kong, Qing-Peng; van der Westhuizen, Francois H; Pitceathly, Robert D S; Thorburn, David R; Lott, Marie T; Wallace, Douglas C; Taylor, Robert W; McFarland, Robert

2012-09-01

The Human Variome Project (HVP) is a global effort to collect and curate all human genetic variation affecting health. Mutations of mitochondrial DNA (mtDNA) are an important cause of neurogenetic disease in humans; however, identification of the pathogenic mutations responsible can be problematic. In this article, we provide explanations as to why and suggest how such difficulties might be overcome. We put forward a case in support of a new Locus Specific Mutation Database (LSDB) implemented using the Leiden Open-source Variation Database (LOVD) system that will not only list primary mutations, but also present the evidence supporting their role in disease. Critically, we feel that this new database should have the capacity to store information on the observed phenotypes alongside the genetic variation, thereby facilitating our understanding of the complex and variable presentation of mtDNA disease. LOVD supports fast queries of both seen and hidden data and allows storage of sequence variants from high-throughput sequence analysis. The LOVD platform will allow construction of a secure mtDNA database; one that can fully utilize currently available data, as well as that being generated by high-throughput sequencing, to link genotype with phenotype enhancing our understanding of mitochondrial disease, with a view to providing better prognostic information. © 2012 Wiley Periodicals, Inc.

Toward a mtDNA Locus-Specific Mutation Database Using the LOVD Platform

PubMed Central

Elson, Joanna L.; Sweeney, Mary G.; Procaccio, Vincent; Yarham, John W.; Salas, Antonio; Kong, Qing-Peng; van der Westhuizen, Francois H.; Pitceathly, Robert D.S.; Thorburn, David R.; Lott, Marie T.; Wallace, Douglas C.; Taylor, Robert W.; McFarland, Robert

2015-01-01

The Human Variome Project (HVP) is a global effort to collect and curate all human genetic variation affecting health. Mutations of mitochondrial DNA (mtDNA) are an important cause of neurogenetic disease in humans; however, identification of the pathogenic mutations responsible can be problematic. In this article, we provide explanations as to why and suggest how such difficulties might be overcome. We put forward a case in support of a new Locus Specific Mutation Database (LSDB) implemented using the Leiden Open-source Variation Database (LOVD) system that will not only list primary mutations, but also present the evidence supporting their role in disease. Critically, we feel that this new database should have the capacity to store information on the observed phenotypes alongside the genetic variation, thereby facilitating our understanding of the complex and variable presentation of mtDNA disease. LOVD supports fast queries of both seen and hidden data and allows storage of sequence variants from high-throughput sequence analysis. The LOVD platform will allow construction of a secure mtDNA database; one that can fully utilize currently available data, as well as that being generated by high-throughput sequencing, to link genotype with phenotype enhancing our understanding of mitochondrial disease, with a view to providing better prognostic information. PMID:22581690

Genetic variation affecting host-parasite interactions: major-effect quantitative trait loci affect the transmission of sigma virus in Drosophila melanogaster.

PubMed

Bangham, Jenny; Knott, Sara A; Kim, Kang-Wook; Young, Robert S; Jiggins, Francis M

2008-09-01

In natural populations, genetic variation affects resistance to disease. Whether that genetic variation comprises lots of small-effect polymorphisms or a small number of large-effect polymorphisms has implications for adaptation, selection and how genetic variation is maintained in populations. Furthermore, how much genetic variation there is, and the genes that underlie this variation, affects models of co-evolution between parasites and their hosts. We are studying the genetic variation that affects the resistance of Drosophila melanogaster to its natural pathogen--the vertically transmitted sigma virus. We have carried out three separate quantitative trait locus mapping analyses to map gene variants on the second chromosome that cause variation in the rate at which males transmit the infection to their offspring. All three crosses identified a locus in a similar chromosomal location that causes a large drop in the rate at which the virus is transmitted. We also found evidence for an additional smaller-effect quantitative trait locus elsewhere on the chromosome. Our data, together with previous experiments on the sigma virus and parasitoid wasps, indicate that the resistance of D. melanogaster to co-evolved pathogens is controlled by a limited number of major-effect polymorphisms.

Significant genetic and phenotypic changes arising from clonal growth of a single spore of an arbuscular mycorrhizal fungus over multiple generations.

PubMed

Ehinger, Martine O; Croll, Daniel; Koch, Alexander M; Sanders, Ian R

2012-11-01

Arbuscular mycorrhizal fungi (AMF) are highly successful plant symbionts. They reproduce clonally producing multinucleate spores. It has been suggested that some AMF harbor genetically different nuclei. However, recent advances in sequencing the Glomus irregulare genome have indicated very low within-fungus polymorphism. We tested the null hypothesis that, with no genetic differences among nuclei, no significant genetic or phenotypic variation would occur among clonal single spore lines generated from one initial AMF spore. Furthermore, no additional variation would be expected in the following generations of single spore lines. Genetic diversity contained in one initial spore repeatedly gave rise to genetically different variants of the fungus with novel phenotypes. The genetic changes represented quantitative changes in allele frequencies, most probably as a result of changes in the frequency of genetic variation partitioned on different nuclei. The genetic and phenotypic variation is remarkable, given that it arose repeatedly from one clonal individual. Our results highlight the dynamic nature of AMF genetics. Even though within-fungus genetic variation is low, some is probably partitioned among nuclei and potentially causes changes in the phenotype. Our results are important for understanding AMF genetics, as well as for researchers and biotechnologists hoping to use AMF genetic diversity for the improvement of AMF inoculum. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Genetic and epigenetic diversity and structure of Phragmites australis from local habitats of the Songnen Prairie using amplified fragment length polymorphism markers.

PubMed

Qiu, T; Jiang, L L; Yang, Y F

2016-08-19

The genetic and epigenetic diversity and structure of naturally occurring Phragmites australis populations occupying two different habitats on a small spatial scale in the Songnen Prairie in northeastern China were investigated by assessing amplified fragment length polymorphisms (AFLPs) and methylation-sensitive amplified polymorphisms (MSAPs) through fluorescent capillary detection. The two groups of P. australis were located in a seasonal waterlogged low-lying and alkalized meadow with a pH of 8-8.5 and in an alkaline patch without accumulated rainwater and with a pH greater than 10. These groups showed high levels of genetic diversity at the habitat level based on the percentage of polymorphic bands (90.32, 82.56%), Nei's gene diversity index (0.262, 0.248), and the Shannon diversity index (0.407, 0.383). Although little is known about the between-habitat genetic differentiation of P. australis on a small spatial scale, our results implied significant genetic differentiation between habitats. Extensive epigenetic diversity within habitats, along with clear differentiation, was found. Specifically, the former habitat (Habitat 1, designated H1) harbored higher levels of genetic and epigenetic diversity than the latter (Habitat 2, designated H2), and population-level diversity was also high. This study represents one of few attempts to predict habitat-based genetic differentiation of reeds on a small scale. These assessments of genetic and epigenetic variation are integral aspects of molecular ecological studies on P. australis. Possible causes for within- and between-habitat genetic and epigenetic variations are discussed.

Imaging genetics of schizophrenia in the post-GWAS era.

PubMed

Arslan, Ayla

2018-01-03

Imaging genetics is a research methodology studying the effect of genetic variation on brain structure, function, behavior, and risk for psychopathology. Since the early 2000s, imaging genetics has been increasingly used in the research of schizophrenia (SZ). SZ is a severe mental disorder with no precise knowledge of its underlying neurobiology, however, new genetic and neurobiological data generate a climate for new avenues. The accumulating data of genome wide association studies (GWAS) continuously decode SZ risk genes. Global neuroimaging consortia produce collections of brain phenotypes from tens of thousands of people. In this context, imaging genetics will be strategically important both for the validation and discovery of SZ related findings. Thus, the study of GWAS supported risk variants as candidate genes to validate by neuroimaging is one trend. The study of epigenetic differences in relation to variations of brain phenotypes and the study of large scale multivariate analysis of genome wide and brain wide associations are other trends. While these studies hold a big potential for understanding the neurobiology of SZ, the problem of reproducibility appears as a major challenge, which requires standardizations in study designs and compensations of methodological limitations such as sensitivity and specificity. On the other hand, advancements of neuroimaging, optical and electron microscopy along with the use of genetically encoded fluorescent probes and robust statistical approaches will not only catalyze integrative methodologies but also will help better design the imaging genetics studies. In this invited paper, I will discuss the current perspective of imaging genetics and emerging opportunities of SZ research. Copyright © 2017 Elsevier Inc. All rights reserved.

The capture of heritable variation for genetic quality through social competition.

PubMed

Wolf, Jason B; Harris, W Edwin; Royle, Nick J

2008-09-01

In theory, females of many species choose mates based on traits that are indicators of male genetic quality. A fundamental question in evolutionary biology is why genetic variation for such indicator traits persists despite strong persistent selection imposed by female preference, which is known as the lek paradox. One potential solution to the lek paradox suggests that the traits that are targets of mate choice should evolve condition-dependent expression and that condition should have a large genetic variance. Condition is expected to exhibit high genetic variance because it is affected by a large number of physiological processes and hence, condition-dependent traits should 'capture' variation contributed by a large number of loci. We suggest that a potentially important cause of variation in condition is competition for limited resources. Here, we discuss a pair of models to analyze the evolutionary genetics of traits affected by success in social competition for resources. We show that competition can contribute to genetic variation of 'competition-dependent' traits that have fundamentally different evolutionary properties than other sources of variation. Competition dependence can make traits honest indicators of genetic quality by revealing the relative competitive ability of males, can provide a component of heritable variation that does not contribute to trait evolution, and can help maintain heritable variation under directional selection. Here we provide a general introduction to the concept of competition dependence and briefly introduce two models to demonstrate the potential evolutionary consequences of competition-dependent trait expression.

Phenotypic and Genetic Variations in Obligate Parthenogenetic Populations of Eriosoma lanigerum Hausmann (Hemiptera: Aphididae).

PubMed

Ruiz-Montoya, L; Zúñiga, G; Cisneros, R; Salinas-Moreno, Y; Peña-Martínez, R; Machkour-M'Rabet, S

2015-12-01

The study of phenotypic and genetic variation of obligate parthenogenetic organisms contributes to an understanding of evolution in the absence of genetic variation produced by sexual reproduction. Eriosoma lanigerum Hausmann undergoes obligate parthenogenesis in Mexico City, Mexico, due to the unavailability of the host plants required for sexual reproduction. We analysed the phenotypic and genetic variation of E. lanigerum in relation to the dry and wet season and plant phenology. Aphids were collected on two occasions per season on a secondary host plant, Pyracantha koidzumii, at five different sites in the southern area of Mexico City, Mexico. Thirteen morphological characteristics were measured from 147 to 276 individuals per site and per season. A multivariate analysis of variance was performed to test the effect of the season, site and their interaction on morphological traits. Morphological variation was summarised using a principal component analysis. Genetic variation was described using six enzymatic loci, four of which were polymorphic. Our study showed that the site and season has a significant effect on morphological trait variation. The largest aphids were recorded during cold temperatures with low relative humidity and when the plant was at the end of the fruiting period. The mean genetic diversity was low (mean H e =  .161), and populations were genetically structured by season and site. Morphological and genetic variations appear to be associated with environmental factors that directly affect aphid development and/or indirectly by host plant phenology.

Copy Number Variation across European Populations

PubMed Central

Chen, Wanting; Hayward, Caroline; Wright, Alan F.; Hicks, Andrew A.; Vitart, Veronique; Knott, Sara; Wild, Sarah H.; Pramstaller, Peter P.; Wilson, James F.; Rudan, Igor; Porteous, David J.

2011-01-01

Genome analysis provides a powerful approach to test for evidence of genetic variation within and between geographical regions and local populations. Copy number variants which comprise insertions, deletions and duplications of genomic sequence provide one such convenient and informative source. Here, we investigate copy number variants from genome wide scans of single nucleotide polymorphisms in three European population isolates, the island of Vis in Croatia, the islands of Orkney in Scotland and the South Tyrol in Italy. We show that whereas the overall copy number variant frequencies are similar between populations, their distribution is highly specific to the population of origin, a finding which is supported by evidence for increased kinship correlation for specific copy number variants within populations. PMID:21829696

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

PubMed Central

Homburger, Julian R.; Green, Eric M.; Caleshu, Colleen; Sunitha, Margaret S.; Taylor, Rebecca E.; Ruppel, Kathleen M.; Metpally, Raghu Prasad Rao; Colan, Steven D.; Michels, Michelle; Day, Sharlene M.; Olivotto, Iacopo; Bustamante, Carlos D.; Dewey, Frederick E.; Ho, Carolyn Y.; Spudich, James A.; Ashley, Euan A.

2016-01-01

Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children.

PubMed

Dhandapani, Mohanapriya Chinambedu; Venkatesan, Vettriselvi; Rengaswamy, Nammalwar Bollam; Gowrishankar, Kalpana; Ekambaram, Sudha; Sengutavan, Prabha; Perumal, Venkatachalam

2017-02-01

Steroid-resistant nephrotic syndrome (SRNS) is found in 10-20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India. Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy-Weinberg equilibrium. Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708). Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children's at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk.

Simulating the spread of selection-driven genotypes using landscape resistance models for desert bighorn sheep.

PubMed

Creech, Tyler G; Epps, Clinton W; Landguth, Erin L; Wehausen, John D; Crowhurst, Rachel S; Holton, Brandon; Monello, Ryan J

2017-01-01

Landscape genetic studies based on neutral genetic markers have contributed to our understanding of the influence of landscape composition and configuration on gene flow and genetic variation. However, the potential for species to adapt to changing landscapes will depend on how natural selection influences adaptive genetic variation. We demonstrate how landscape resistance models can be combined with genetic simulations incorporating natural selection to explore how the spread of adaptive variation is affected by landscape characteristics, using desert bighorn sheep (Ovis canadensis nelsoni) in three differing regions of the southwestern United States as an example. We conducted genetic sampling and least-cost path modeling to optimize landscape resistance models independently for each region, and then simulated the spread of an adaptive allele favored by selection across each region. Optimized landscape resistance models differed between regions with respect to landscape variables included and their relationships to resistance, but the slope of terrain and the presence of water barriers and major roads had the greatest impacts on gene flow. Genetic simulations showed that differences among landscapes strongly influenced spread of adaptive genetic variation, with faster spread (1) in landscapes with more continuously distributed habitat and (2) when a pre-existing allele (i.e., standing genetic variation) rather than a novel allele (i.e., mutation) served as the source of adaptive genetic variation. The combination of landscape resistance models and genetic simulations has broad conservation applications and can facilitate comparisons of adaptive potential within and between landscapes.

Simulating the spread of selection-driven genotypes using landscape resistance models for desert bighorn sheep

PubMed Central

Epps, Clinton W.; Landguth, Erin L.; Wehausen, John D.; Crowhurst, Rachel S.; Holton, Brandon; Monello, Ryan J.

2017-01-01

Landscape genetic studies based on neutral genetic markers have contributed to our understanding of the influence of landscape composition and configuration on gene flow and genetic variation. However, the potential for species to adapt to changing landscapes will depend on how natural selection influences adaptive genetic variation. We demonstrate how landscape resistance models can be combined with genetic simulations incorporating natural selection to explore how the spread of adaptive variation is affected by landscape characteristics, using desert bighorn sheep (Ovis canadensis nelsoni) in three differing regions of the southwestern United States as an example. We conducted genetic sampling and least-cost path modeling to optimize landscape resistance models independently for each region, and then simulated the spread of an adaptive allele favored by selection across each region. Optimized landscape resistance models differed between regions with respect to landscape variables included and their relationships to resistance, but the slope of terrain and the presence of water barriers and major roads had the greatest impacts on gene flow. Genetic simulations showed that differences among landscapes strongly influenced spread of adaptive genetic variation, with faster spread (1) in landscapes with more continuously distributed habitat and (2) when a pre-existing allele (i.e., standing genetic variation) rather than a novel allele (i.e., mutation) served as the source of adaptive genetic variation. The combination of landscape resistance models and genetic simulations has broad conservation applications and can facilitate comparisons of adaptive potential within and between landscapes. PMID:28464013

Genetic variability among Trichuris ovis isolates from different hosts in Guangdong Province, China revealed by sequences of three mitochondrial genes.

PubMed

Wang, Yan; Liu, Guo-Hua; Li, Jia-Yuan; Xu, Min-Jun; Ye, Yong-Gang; Zhou, Dong-Hui; Song, Hui-Qun; Lin, Rui-Qing; Zhu, Xing-Quan

2013-02-01

This study examined sequence variation in three mitochondrial DNA (mtDNA) regions, namely cytochrome c oxidase subunit 1 (cox1), NADH dehydrogenase subunit 5 (nad5) and cytochrome b (cytb), among Trichuris ovis isolates from different hosts in Guangdong Province, China. A portion of the cox1 (pcox1), nad5 (pnad5) and cytb (pcytb) genes was amplified separately from individual whipworms by PCR, and was subjected to sequencing from both directions. The size of the sequences of pcox1, pnad5 and pcytb was 618, 240 and 464 bp, respectively. Although the intra-specific sequence variations within T. ovis were 0-0.8% for pcox1, 0-0.8% for pnad5 and 0-1.9% for pcytb, the inter-specific sequence differences among members of the genus Trichuris were significantly higher, being 24.3-26.5% for pcox1, 33.7-56.4% for pnad5 and 24.8-26.1% for pcytb, respectively. Phylogenetic analyses using combined sequences of pcox1, pnad5 and pcytb, with three different computational algorithms (maximum likelihood, maximum parsimony and Bayesian inference), indicated that all of the T. ovis isolates grouped together with high statistical support. These findings demonstrated the existence of intra-specific variation in mtDNA sequences among T. ovis isolates from different hosts, and have implications for studying molecular epidemiology and population genetics of T. ovis.

Genetic parameters for uniformity of harvest weight and body size traits in the GIFT strain of Nile tilapia.

PubMed

Marjanovic, Jovana; Mulder, Han A; Khaw, Hooi L; Bijma, Piter

2016-06-10

Animal breeding programs have been very successful in improving the mean levels of traits through selection. However, in recent decades, reducing the variability of trait levels between individuals has become a highly desirable objective. Reaching this objective through genetic selection requires that there is genetic variation in the variability of trait levels, a phenomenon known as genetic heterogeneity of environmental (residual) variance. The aim of our study was to investigate the potential for genetic improvement of uniformity of harvest weight and body size traits (length, depth, and width) in the genetically improved farmed tilapia (GIFT) strain. In order to quantify the genetic variation in uniformity of traits and estimate the genetic correlations between level and variance of the traits, double hierarchical generalized linear models were applied to individual trait values. Our results showed substantial genetic variation in uniformity of all analyzed traits, with genetic coefficients of variation for residual variance ranging from 39 to 58 %. Genetic correlation between trait level and variance was strongly positive for harvest weight (0.60 ± 0.09), moderate and positive for body depth (0.37 ± 0.13), but not significantly different from 0 for body length and width. Our results on the genetic variation in uniformity of harvest weight and body size traits show good prospects for the genetic improvement of uniformity in the GIFT strain. A high and positive genetic correlation was estimated between level and variance of harvest weight, which suggests that selection for heavier fish will also result in more variation in harvest weight. Simultaneous improvement of harvest weight and its uniformity will thus require index selection.

Phylogeny of Fomitopsis pinicola: A species complex

Treesearch

John Haight; Gary A. Laursen; Jessie A. Glaeser; D. Lee Taylor

2016-01-01

Fungal species with a broad distribution may exhibit considerable genetic variation over their geographic ranges. Variation may develop among populations based on geographic isolation, lack of migration, and genetic drift, though this genetic variation may not always be evident when examining phenotypic characters. Fomitopsis pinicola is an...

Genetic variation of Taenia pisiformis collected from Sichuan, China, based on the mitochondrial cytochrome B gene.

PubMed

Yang, Deying; Ren, Yongjun; Fu, Yan; Xie, Yue; Nie, Huaming; Nong, Xiang; Gu, Xiaobin; Wang, Shuxian; Peng, Xuerong; Yang, Guangyou

2013-08-01

Taenia pisiformis is one of the most important parasites of canines and rabbits. T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit breeding, which results in huge economic losses. In this study, the genetic variation of T. pisiformis was determined in Sichuan Province, China. Fragments of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53 isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic variation derived from intra-region. FST and Nm values suggested that 53 isolates were not genetically differentiated and had low levels of genetic diversity. Neutrality indices of the cytb sequences showed the evolution of T. pisiformis followed a neutral mode. Phylogenetic analysis revealed no correlation between phylogeny and geographic distribution. These findings indicate that 53 isolates of T. pisiformis keep a low genetic variation, which provide useful knowledge for monitoring changes in parasite populations for future control strategies.

GENETIC VARIATION IN BABOON CRANIOFACIAL SEXUAL DIMORPHISM

PubMed Central

Willmore, Katherine E.; Roseman, Charles C.; Rogers, Jeffrey; Richtsmeier, Joan T.; Cheverud, James M.

2010-01-01

Sexual dimorphism is a widespread phenomenon and contributes greatly to intraspecies variation. Despite a long history of active research, the genetic basis of dimorphism for complex traits remains unknown. Understanding the sex-specific differences in genetic architecture for cranial traits in a highly dimorphic species could identify possible mechanisms through which selection acts to produce dimorphism. Using distances calculated from three-dimensional landmark data from CT scans of 402 baboon skulls from a known genealogy, we estimated genetic variance parameters in both sexes to determine the presence of gene-by-sex (G × S) interactions and X-linked heritability. We hypothesize that traits exhibiting the greatest degree of sexual dimorphism (facial traits in baboons) will demonstrate either stronger G × S interactions or X-linked effects. We found G × S interactions and X-linked effects for a few measures that span the areas connecting the face to the neurocranium but for no traits restricted to the face. This finding suggests that facial traits will have a limited response to selection for further evolution of dimorphism in this population. We discuss the implications of our results with respect to the origins of cranial sexual dimorphism in this baboon sample, and how the genetic architecture of these traits affects their potential for future evolution. PMID:19210535

Undergraduates Achieve Learning Gains in Plant Genetics through Peer Teaching of Secondary Students

PubMed Central

Chrispeels, H. E.; Klosterman, M. L.; Martin, J. B.; Lundy, S. R.; Watkins, J. M.; Gibson, C. L.

2014-01-01

This study tests the hypothesis that undergraduates who peer teach genetics will have greater understanding of genetic and molecular biology concepts as a result of their teaching experiences. Undergraduates enrolled in a non–majors biology course participated in a service-learning program in which they led middle school (MS) or high school (HS) students through a case study curriculum to discover the cause of a green tomato variant. The curriculum explored plant reproduction and genetic principles, highlighting variation in heirloom tomato fruits to reinforce the concept of the genetic basis of phenotypic variation. HS students were taught additional activities related to mole­cular biology techniques not included in the MS curriculum. We measured undergraduates’ learning outcomes using pre/postteaching content assessments and the course final exam. Undergraduates showed significant gains in understanding of topics related to the curriculum they taught, compared with other course content, on both types of assessments. Undergraduates who taught HS students scored higher on questions specific to the HS curriculum compared with undergraduates who taught MS students, despite identical lecture content, on both types of assessments. These results indicate the positive effect of service-learning peer-teaching experiences on undergraduates’ content knowledge, even for non–science major students. PMID:25452487

Variation in sclerophylly among Iberian populations of Quercus coccifera L. is associated with genetic differentiation across contrasting environments.

PubMed

Rubio de Casas, R; Vargas, P; Pérez-Corona, E; Cano, E; Manrique, E; García-Verdugo, C; Balaguer, L

2009-05-01

Evergreen oaks are an emblematic element of the Mediterranean vegetation and have a leaf phenotype that seems to have remained unchanged since the Miocene. We hypothesise that variation of the sclerophyll phenotype among Iberian populations of Quercus coccifera is partly due to an ulterior process of ecotypic differentiation. We analysed the genetic structure of nine Iberian populations using ISSR fingerprints, and their leaf phenotypes using mean and intracanopy plasticity values of eight morphological (leaf angle, area, spinescence, lobation and specific area) and biochemical traits (VAZ pool, chlorophyll and beta-carotene content). Climate and soil were also characterised at the population sites. Significant genetic and phenotypic differences were found among populations and between NE Iberia and the rest of the populations of the peninsula. Mean phenotypes showed a strong and independent correlation with both genetic and geographic distances. Northeastern plants were smaller, less plastic, with smaller, spinier and thicker leaves, a phenotype consistent with the stressful conditions that prevailed in the steppe environments of the refugia within this geographic area during glaciations. These genetic, phenotypic, geographic and environmental patterns are consistent with previously reported palaeoecological and common evidence. Such consistency leads us to conclude that there has been a Quaternary divergence within the sclerophyllous syndrome that was at least partially driven by ecological factors.

Variation in healthcare services for specialist genetic testing and implications for planning genetic services: the example of inherited retinal dystrophy in the English NHS.

PubMed

Harrison, Mark; Birch, Stephen; Eden, Martin; Ramsden, Simon; Farragher, Tracey; Payne, Katherine; Hall, Georgina; Black, Graeme Cm

2015-04-01

This study aims to identify and quantify the extent of current variation in service provision of a genetic testing service for dominant and X-linked retinal dystrophies in the English National Health Service (NHS). National audit data (all test requests and results (n = 1839) issued between 2003 and 2011) and survey of English regional genetic testing services were used. Age- and gender-adjusted standardised testing rates were calculated using indirect standardisation, and survey responses were transcribed verbatim and data collated and summarised. The cumulative incidence rate of testing in England was 4.5 per 100,000 population for males and 2.6 per 100,000 population for females. The standardised testing rate (STR) varied widely between regions of England, being particularly low in the North-east (STR 0.485), with half as many tests as expected based on the size and demographic distribution of the population and high in the South-east (STR 1.355), with 36 % more tests than expected. Substantial and significantly different rates of testing were found between regional populations. Specific policy mechanisms to promote, monitor and evaluate the regional distribution of access to genetic and genomic testing are required. However, commissioners will require information on the scope and role of genetic services and the population at risk of the conditions for which patients are tested.

Reduced representation genome sequencing reveals patterns of genetic diversity and selection in apple.

PubMed

Ma, Baiquan; Liao, Liao; Peng, Qian; Fang, Ting; Zhou, Hui; Korban, Schuyler S; Han, Yuepeng

2017-03-01

Identifying DNA sequence variations is a fundamental step towards deciphering the genetic basis of traits of interest. Here, a total of 20 cultivated and 10 wild apples were genotyped using specific-locus amplified fragment sequencing, and 39,635 single nucleotide polymorphisms with no missing genotypes and evenly distributed along the genome were selected to investigate patterns of genome-wide genetic variations between cultivated and wild apples. Overall, wild apples displayed higher levels of genetic diversity than cultivated apples. Linkage disequilibrium (LD) decays were observed quite rapidly in cultivated and wild apples, with an r 2 -value below 0.2 at 440 and 280 bp, respectively. Moreover, bidirectional gene flow and different distribution patterns of LD blocks were detected between domesticated and wild apples. Most LD blocks unique to cultivated apples were located within QTL regions controlling fruit quality, thus suggesting that fruit quality had probably undergone selection during apple domestication. The genome of the earliest cultivated apple in China, Nai, was highly similar to that of Malus sieversii, and contained a small portion of genetic material from other wild apple species. This suggested that introgression could have been an important driving force during initial domestication of apple. These findings will facilitate future breeding and genetic dissection of complex traits in apple. © 2017 Institute of Botany, Chinese Academy of Sciences.

Culture, Threat, and Mental Illness Stigma: Identifying Culture-Specific Threat among Chinese-American Groups

PubMed Central

Purdie-Vaughns, Valerie; Kotabe, Hiroki; Link, Bruce G.; Saw, Anne; Wong, Gloria; Phelan, Jo C.

2014-01-01

We incorporate anthropological insights into a stigma framework to elucidate the role of culture in threat perception and stigma among Chinese groups. Prior work suggests that genetic contamination that jeopardizes the extension of one’s family lineage may comprise a culture-specific threat among Chinese groups. In Study 1, a national survey conducted from 2002–2003 assessed cultural differences in mental illness stigma and perceptions of threat in 56 Chinese-Americans and 589 European-Americans. Study 2 sought to empirically test this culture-specific threat of genetic contamination to lineage via a memory paradigm. Conducted from June to August 2010, 48 Chinese-American and 37 European-American university students in New York City read vignettes containing content referring to lineage or non-lineage concerns. Half the participants in each ethnic group were assigned to a condition in which the illness was likely to be inherited (genetic condition) and the rest read that the illness was unlikely to be inherited (non-genetic condition). Findings from Study 1 and 2 were convergent. In Study 1, culture-specific threat to lineage predicted cultural variation in stigma independently and after accounting for other forms of threat. In Study 2, Chinese-Americans in the genetic condition were more likely to accurately recall and recognize lineage content than the Chinese-Americans in the non-genetic condition, but that memorial pattern was not found for non-lineage content. The identification of this culture-specific threat among Chinese groups has direct implications for culturally-tailored anti-stigma interventions. Further, this framework might be implemented across other conditions and cultural groups to reduce stigma across cultures. PMID:23702210

Culture, threat, and mental illness stigma: identifying culture-specific threat among Chinese-American groups.

PubMed

Yang, Lawrence H; Purdie-Vaughns, Valerie; Kotabe, Hiroki; Link, Bruce G; Saw, Anne; Wong, Gloria; Phelan, Jo C

2013-07-01

We incorporate anthropological insights into a stigma framework to elucidate the role of culture in threat perception and stigma among Chinese groups. Prior work suggests that genetic contamination that jeopardizes the extension of one's family lineage may comprise a culture-specific threat among Chinese groups. In Study 1, a national survey conducted from 2002 to 2003 assessed cultural differences in mental illness stigma and perceptions of threat in 56 Chinese-Americans and 589 European-Americans. Study 2 sought to empirically test this culture-specific threat of genetic contamination to lineage via a memory paradigm. Conducted from June to August 2010, 48 Chinese-American and 37 European-American university students in New York City read vignettes containing content referring to lineage or non-lineage concerns. Half the participants in each ethnic group were assigned to a condition in which the illness was likely to be inherited (genetic condition) and the rest read that the illness was unlikely to be inherited (non-genetic condition). Findings from Study 1 and 2 were convergent. In Study 1, culture-specific threat to lineage predicted cultural variation in stigma independently and after accounting for other forms of threat. In Study 2, Chinese-Americans in the genetic condition were more likely to accurately recall and recognize lineage content than the Chinese-Americans in the non-genetic condition, but that memorial pattern was not found for non-lineage content. The identification of this culture-specific threat among Chinese groups has direct implications for culturally-tailored anti-stigma interventions. Further, this framework might be implemented across other conditions and cultural groups to reduce stigma across cultures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Climates Past, Present, and Yet-to-Come Shape Climate Change Vulnerabilities.

PubMed

Nadeau, Christopher P; Urban, Mark C; Bridle, Jon R

2017-10-01

Climate change is altering life at multiple scales, from genes to ecosystems. Predicting the vulnerability of populations to climate change is crucial to mitigate negative impacts. We suggest that regional patterns of spatial and temporal climatic variation scaled to the traits of an organism can predict where and why populations are most vulnerable to climate change. Specifically, historical climatic variation affects the sensitivity and response capacity of populations to climate change by shaping traits and the genetic variation in those traits. Present and future climatic variation can affect both climate change exposure and population responses. We provide seven predictions for how climatic variation might affect the vulnerability of populations to climate change and suggest key directions for future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of a specific intronic PEAR1 gene variant associated with greater platelet aggregability and protein expression

PubMed Central

Yanek, Lisa R.; Yang, Xiao Ping; Mathias, Rasika; Herrera-Galeano, J. Enrique; Suktitipat, Bhoom; Qayyum, Rehan; Johnson, Andrew D.; Chen, Ming-Huei; Tofler, Geoffrey H.; Ruczinski, Ingo; Friedman, Alan D.; Gylfason, Arnaldur; Thorsteinsdottir, Unnur; Bray, Paul F.; O'Donnell, Christopher J.; Becker, Diane M.; Becker, Lewis C.

2011-01-01

Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for ≤ 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 × 10−8) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10−27) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10−5). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10−6) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the G allele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype. PMID:21791418

Heritability, covariation and natural selection on 24 traits of common evening primrose (Oenothera biennis) from a field experiment.

PubMed

Johnson, M T J; Agrawal, A A; Maron, J L; Salminen, J-P

2009-06-01

This study explored genetic variation and co-variation in multiple functional plant traits. Our goal was to characterize selection, heritabilities and genetic correlations among different types of traits to gain insight into the evolutionary ecology of plant populations and their interactions with insect herbivores. In a field experiment, we detected significant heritable variation for each of 24 traits of Oenothera biennis and extensive genetic covariance among traits. Traits with diverse functions formed several distinct groups that exhibited positive genetic covariation with each other. Genetic variation in life-history traits and secondary chemistry together explained a large proportion of variation in herbivory (r(2) = 0.73). At the same time, selection acted on lifetime biomass, life-history traits and two secondary compounds of O. biennis, explaining over 95% of the variation in relative fitness among genotypes. The combination of genetic covariances and directional selection acting on multiple traits suggests that adaptive evolution of particular traits is constrained, and that correlated evolution of groups of traits will occur, which is expected to drive the evolution of increased herbivore susceptibility. As a whole, our study indicates that an examination of genetic variation and covariation among many different types of traits can provide greater insight into the evolutionary ecology of plant populations and plant-herbivore interactions.

Sexually antagonistic selection on genetic variation underlying both male and female same-sex sexual behavior.

PubMed

Berger, David; You, Tao; Minano, Maravillas R; Grieshop, Karl; Lind, Martin I; Arnqvist, Göran; Maklakov, Alexei A

2016-05-13

Intralocus sexual conflict, arising from selection for different alleles at the same locus in males and females, imposes a constraint on sex-specific adaptation. Intralocus sexual conflict can be alleviated by the evolution of sex-limited genetic architectures and phenotypic expression, but pleiotropic constraints may hinder this process. Here, we explored putative intralocus sexual conflict and genetic (co)variance in a poorly understood behavior with near male-limited expression. Same-sex sexual behaviors (SSBs) generally do not conform to classic evolutionary models of adaptation but are common in male animals and have been hypothesized to result from perception errors and selection for high male mating rates. However, perspectives incorporating sex-specific selection on genes shared by males and females to explain the expression and evolution of SSBs have largely been neglected. We performed two parallel sex-limited artificial selection experiments on SSB in male and female seed beetles, followed by sex-specific assays of locomotor activity and male sex recognition (two traits hypothesized to be functionally related to SSB) and adult reproductive success (allowing us to assess fitness consequences of genetic variance in SSB and its correlated components). Our experiments reveal both shared and sex-limited genetic variance for SSB. Strikingly, genetically correlated responses in locomotor activity and male sex-recognition were associated with sexually antagonistic fitness effects, but these effects differed qualitatively between male and female selection lines, implicating intralocus sexual conflict at both male- and female-specific genetic components underlying SSB. Our study provides experimental support for the hypothesis that widespread pleiotropy generates pervasive intralocus sexual conflict governing the expression of SSBs, suggesting that SSB in one sex can occur due to the expression of genes that carry benefits in the other sex.

Genetic short stature.

PubMed

Grunauer, Michelle; Jorge, Alexander A L

2018-02-01

Adult height and growth patterns are largely genetically programmed. Studies in twins have indicated that the heritability of height is high (>80%), suggesting that genetic variation is the main determinant of stature. Height exhibits a normal (Gaussian) distribution according to sex, age, and ancestry. Short stature is usually defined as a height which is 2 standard deviations (S.D.) less than the mean height of a specific population. This definition includes 2.3% of the population and usually includes healthy individuals. In this group of short stature non-syndromic conditions, the genetic influence occurs polygenically or oligogenically. As a rule, each common genetic variant accounts for a small effect (1mm) on individual height variation. Recently, several studies demonstrated that some rare variants can cause greater effect on height, without causing a syndromic condition. In more extreme cases, height SDS below 2.5 or 3 (which would comprise approximately 0.6 and 0.1% of the population, respectively) is frequently associated with syndromic conditions and are usually caused by a monogenic defect. More than 1,000 inherited/genetic diseases have growth disorder as an important phenotype. These conditions are usually responsible for syndromic short stature. In the coming years, we expect to discover several genetic causes of short stature, thereby explaining the phenotype of what we currently classify as short stature of unknown cause. These discoveries will have a profound impact on the follow-up and treatment of these children. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Hybridization and Evolutionary Constraints on Secondary Metabolites: The Genetic Architecture of Phenylpropanoids in European Populus Species

PubMed Central

Caseys, Celine; Stritt, Christoph; Glauser, Gaetan; Blanchard, Thierry; Lexer, Christian

2015-01-01

The mechanisms responsible for the origin, maintenance and evolution of plant secondary metabolite diversity remain largely unknown. Decades of phenotypic studies suggest hybridization as a key player in generating chemical diversity in plants. Knowledge of the genetic architecture and selective constraints of phytochemical traits is key to understanding the effects of hybridization on plant chemical diversity and ecological interactions. Using the European Populus species P. alba (White poplar) and P. tremula (European aspen) and their hybrids as a model, we examined levels of inter- and intraspecific variation, heritabilities, phenotypic correlations, and the genetic architecture of 38 compounds of the phenylpropanoid pathway measured by liquid chromatography and mass spectrometry (UHPLC-MS). We detected 41 quantitative trait loci (QTL) for chlorogenic acids, salicinoids and flavonoids by genetic mapping in natural hybrid crosses. We show that these three branches of the phenylpropanoid pathway exhibit different geographic patterns of variation, heritabilities, and genetic architectures, and that they are affected differently by hybridization and evolutionary constraints. Flavonoid abundances present high species specificity, clear geographic structure, and strong genetic determination, contrary to salicinoids and chlorogenic acids. Salicinoids, which represent important defence compounds in Salicaceae, exhibited pronounced genetic correlations on the QTL map. Our results suggest that interspecific phytochemical differentiation is concentrated in downstream sections of the phenylpropanoid pathway. In particular, our data point to glycosyltransferase enzymes as likely targets of rapid evolution and interspecific differentiation in the ‘model forest tree’ Populus. PMID:26010156

Effects of hybridization and evolutionary constraints on secondary metabolites: the genetic architecture of phenylpropanoids in European populus species.

PubMed

Caseys, Celine; Stritt, Christoph; Glauser, Gaetan; Blanchard, Thierry; Lexer, Christian

2015-01-01

The mechanisms responsible for the origin, maintenance and evolution of plant secondary metabolite diversity remain largely unknown. Decades of phenotypic studies suggest hybridization as a key player in generating chemical diversity in plants. Knowledge of the genetic architecture and selective constraints of phytochemical traits is key to understanding the effects of hybridization on plant chemical diversity and ecological interactions. Using the European Populus species P. alba (White poplar) and P. tremula (European aspen) and their hybrids as a model, we examined levels of inter- and intraspecific variation, heritabilities, phenotypic correlations, and the genetic architecture of 38 compounds of the phenylpropanoid pathway measured by liquid chromatography and mass spectrometry (UHPLC-MS). We detected 41 quantitative trait loci (QTL) for chlorogenic acids, salicinoids and flavonoids by genetic mapping in natural hybrid crosses. We show that these three branches of the phenylpropanoid pathway exhibit different geographic patterns of variation, heritabilities, and genetic architectures, and that they are affected differently by hybridization and evolutionary constraints. Flavonoid abundances present high species specificity, clear geographic structure, and strong genetic determination, contrary to salicinoids and chlorogenic acids. Salicinoids, which represent important defence compounds in Salicaceae, exhibited pronounced genetic correlations on the QTL map. Our results suggest that interspecific phytochemical differentiation is concentrated in downstream sections of the phenylpropanoid pathway. In particular, our data point to glycosyltransferase enzymes as likely targets of rapid evolution and interspecific differentiation in the 'model forest tree' Populus.

Open Access Resources for Genome Wide Association Studies (GWAS) in rice (Oryza sativa) illustrate the power of population-specific mapping

USDA-ARS?s Scientific Manuscript database

Increasing food production is essential to meet the demands of a growing human population, with its rising income levels and nutritional expectations. New sources of genetic variation are key to enhancing the productivity, sustainability and resilience of crop varieties and agricultural systems that...

Patterns of Genetic Variation among Populations of the Asian Longhorned Beetle in China and Korea

USDA-ARS?s Scientific Manuscript database

Central to the study of invasive species is identifying source populations in their native ranges. Source populations of invasive species can provide important information about species life cycles, host use and species-specific predators and parasites which could be deployed in a pest control prog...

Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylas genes with biochemical measures of vitamin K status

USDA-ARS?s Scientific Manuscript database

Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity ...

Effects of Sex Chromosome Aneuploidies on Brain Development: Evidence from Neuroimaging Studies

ERIC Educational Resources Information Center

Lenroot, Rhoshel K.; Lee, Nancy Raitano; Giedd, Jay N.

2009-01-01

Variation in the number of sex chromosomes is a relatively common genetic condition, affecting as many as 1/400 individuals. The sex chromosome aneuploidies (SCAs) are associated with characteristic behavioral and cognitive phenotypes, although the degree to which specific individuals are affected can fall within a wide range. Understanding the…

Advances in molecular identification, taxonomy, genetic variation and diagnosis of Toxocara spp.

PubMed

Chen, Jia; Zhou, Dong-Hui; Nisbet, Alasdair J; Xu, Min-Jun; Huang, Si-Yang; Li, Ming-Wei; Wang, Chun-Ren; Zhu, Xing-Quan

2012-10-01

The genus Toxocara contains parasitic nematodes of human and animal health significance, such as Toxocara canis, Toxocara cati and Toxocara vitulorum. T. canis and T. cati are among the most prevalent parasites of dogs and cats with a worldwide distribution. Human infection with T. canis and T. cati, which can cause a number of clinical manifestations such as visceral larva migrans (VLMs), ocular larva migrans (OLMs), eosinophilic meningoencephalitis (EME), covert toxocariasis (CT) and neurotoxocariasis, is considered the most prevalent neglected helminthiasis in industrialized countries. The accurate identification Toxocara spp. and their unequivocal differentiation from each other and from other ascaridoid nematodes causing VLMs and OLMs has important implications for studying their taxonomy, epidemiology, population genetics, diagnosis and control. Due to the limitations of traditional (morphological) approaches for identification and diagnosis of Toxocara spp., PCR-based techniques utilizing a range of genetic markers in the nuclear and mitochondrial genomes have been developed as useful alternative approaches because of their high sensitivity, specificity, rapidity and utility. In this article, we summarize the current state of knowledge and advances in molecular identification, taxonomy, genetic variation and diagnosis of Toxocara spp. with prospects for further studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetic variation in food choice behaviour of amino acid-deprived Drosophila.

PubMed

Toshima, Naoko; Hara, Chieko; Scholz, Claus-Jürgen; Tanimura, Teiichi

2014-10-01

To understand homeostatic regulation in insects, we need to understand the mechanisms by which they respond to external stimuli to maintain the internal milieu. Our previous study showed that Drosophila melanogaster exhibit specific amino acid preferences. Here, we used the D.melanogaster Genetic Reference Panel (DGRP), which is comprised of multiple inbred lines derived from a natural population, to examine how amino acid preference changes depending on the internal nutritional state in different lines. We performed a two-choice preference test and observed genetic variations in the response to amino acid deprivation. For example, a high-responding line showed an enhanced preference for amino acids even after only 1day of deprivation and responded to a fairly low concentration of amino acids. Conversely, a low-responding line showed no increased preference for amino acids after deprivation. We compared the gene expression profiles between selected high- and the low-responding lines and performed SNP analyses. We found several groups of genes putatively involved in altering amino acid preference. These results will contribute to future studies designed to explore how the genetic architecture of an organism evolves to adapt to different nutritional environments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evolutionary potential of root chemical defense: genetic correlations with shoot chemistry and plant growth.

PubMed

Parker, J D; Salminen, J-P; Agrawal, Anurag A

2012-08-01

Root herbivores can affect plant fitness, and roots often contain the same secondary metabolites that act as defenses in shoots, but the ecology and evolution of root chemical defense have been little investigated. Here, we investigated genetic variance, heritability, and correlations among defensive phenolic compounds in shoot vs. root tissues of common evening primrose, Oenothera biennis. Across 20 genotypes, there were roughly similar concentrations of total phenolics in shoots vs. roots, but the allocation of particular phenolics to shoots vs. roots varied along a continuum of genotype growth rate. Slow-growing genotypes allocated 2-fold more of the potential pro-oxidant oenothein B to shoots than roots, whereas fast-growing genotypes had roughly equivalent above and belowground concentrations. Phenolic concentrations in both roots and shoots were strongly heritable, with mostly positive patterns of genetic covariation. Nonetheless, there was genotype-specific variation in the presence/absence of two major ellagitannins (oenothein A and its precursor oenothein B), indicating two different chemotypes based on alterations in this chemical pathway. Overall, the presence of strong genetic variation in root defenses suggests ample scope for the evolution of these compounds as defenses against root herbivores.

Are SNP-Smoking Association Studies Needed in Controls? DNA Repair Gene Polymorphisms and Smoking Intensity

PubMed Central

Verde, Zoraida; Reinoso, Luis; Chicharro, Luis Miguel; Resano, Pilar; Sánchez-Hernández, Ignacio; Rodríguez González-Moro, Jose Miguel; Bandrés, Fernando

2015-01-01

Variations in tobacco-related cancers, incidence and prevalence reflect differences in tobacco consumption in addition to genetic factors. Besides, genes related to lung cancer risk could be related to smoking behavior. Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Common problems in genetic association studies, such as presence of gene-by-environment (G x E) correlation in the population, may reduce the validity of these designs. The main purpose of this study was to evaluate the independence assumption for selected SNPs and smoking behaviour in a cohort of 320 healthy Spanish smokers. We found an association between the wild type alleles of XRCC3 Thr241Met or KLC3 Lys751Gln and greater smoking intensity (OR = 12.98, 95% CI = 2.86–58.82 and OR=16.90, 95% CI=2.09-142.8; respectively). Although preliminary, the results of our study provide evidence that genetic variations in DNA-repair genes may influence both smoking habits and the development of lung cancer. Population-specific G x E studies should be carried out when genetic and environmental factors interact to cause the disease. PMID:26017978

Within Host Evolution Selects for a Dominant Genotype of Mycobacterium tuberculosis while T Cells Increase Pathogen Genetic Diversity.

PubMed

Copin, Richard; Wang, Xueying; Louie, Eddie; Escuyer, Vincent; Coscolla, Mireia; Gagneux, Sebastien; Palmer, Guy H; Ernst, Joel D

2016-12-01

Molecular epidemiological assessments, drug treatment optimization, and development of immunological interventions all depend on understanding pathogen adaptation and genetic variation, which differ for specific pathogens. Mycobacterium tuberculosis is an exceptionally successful human pathogen, yet beyond knowledge that this bacterium has low overall genomic variation but acquires drug resistance mutations, little is known of the factors that drive its population genomic characteristics. Here, we compared the genetic diversity of the bacteria that established infection to the bacterial populations obtained from infected tissues during murine M. tuberculosis pulmonary infection and human disseminated M. bovis BCG infection. We found that new mutations accumulate during in vitro culture, but that in vivo, purifying selection against new mutations dominates, indicating that M. tuberculosis follows a dominant lineage model of evolution. Comparing bacterial populations passaged in T cell-deficient and immunocompetent mice, we found that the presence of T cells is associated with an increase in the diversity of the M. tuberculosis genome. Together, our findings put M. tuberculosis genetic evolution in a new perspective and clarify the impact of T cells on sequence diversity of M. tuberculosis.

Mutation scanning analysis of genetic variation within and among Echinococcus species: implications and future prospects.

PubMed

Jabbar, Abdul; Gasser, Robin B

2013-07-01

Adult tapeworms of the genus Echinococcus (family Taeniidae) occur in the small intestines of carnivorous definitive hosts and are transmitted to particular intermediate mammalian hosts, in which they develop as fluid-filled larvae (cysts) in internal organs (usually lung and liver), causing the disease echinococcosis. Echinococcus species are of major medical importance and also cause losses to the meat and livestock industries, mainly due to the condemnation of infected offal. Decisions regarding the treatment and control of echinococcosis rely on the accurate identification of species and population variants (strains). Conventional, phenetic methods for specific identification have some significant limitations. Despite advances in the development of molecular tools, there has been limited application of mutation scanning methods to species of Echinococcus. Here, we briefly review key genetic markers used for the identification of Echinococcus species and techniques for the analysis of genetic variation within and among populations, and the diagnosis of echinococcosis. We also discuss the benefits of utilizing mutation scanning approaches to elucidate the population genetics and epidemiology of Echinococcus species. These benefits are likely to become more evident following the complete characterization of the genomes of E. granulosus and E. multilocularis.

A Geographic Cline of Skull and Brain Morphology among Individuals of European Ancestry

PubMed Central

Bakken, Trygve E.; Dale, Anders M.; Schork, Nicholas J.

2011-01-01

Background Human skull and brain morphology are strongly influenced by genetic factors, and skull size and shape vary worldwide. However, the relationship between specific brain morphology and genetically-determined ancestry is largely unknown. Methods We used two independent data sets to characterize variation in skull and brain morphology among individuals of European ancestry. The first data set is a historical sample of 1,170 male skulls with 37 shape measurements drawn from 27 European populations. The second data set includes 626 North American individuals of European ancestry participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with magnetic resonance imaging, height and weight, neurological diagnosis, and genome-wide single nucleotide polymorphism (SNP) data. Results We found that both skull and brain morphological variation exhibit a population-genetic fingerprint among individuals of European ancestry. This fingerprint shows a Northwest to Southeast gradient, is independent of body size, and involves frontotemporal cortical regions. Conclusion Our findings are consistent with prior evidence for gene flow in Europe due to historical population movements and indicate that genetic background should be considered in studies seeking to identify genes involved in human cortical development and neuropsychiatric disease. PMID:21849792

High MHC diversity maintained by balancing selection in an otherwise genetically monomorphic mammal

PubMed Central

Aguilar, Andres; Roemer, Gary; Debenham, Sally; Binns, Matthew; Garcelon, David; Wayne, Robert K.

2004-01-01

The San Nicolas Island fox (Urocyon littoralis dickeyi) is genetically the most monomorphic sexually reproducing animal population yet reported and has no variation in hypervariable genetic markers. Such low levels of variation imply lower resistance to pathogens, reduced fitness, and problems in distinguishing kin from non-kin. In vertebrates, the MHC contains genes that influence disease resistance and kin recognition and may be under intense balancing selection in some populations. Hence, genetic variation at the MHC might persist despite the extreme monomorphism shown by neutral markers. We examine variation of five loci within the MHC of San Nicolas Island foxes and find remarkably high levels of variation. Further, we show by simulation that genetic monomorphism at neutral loci and high MHC variation could arise only through an extreme population bottleneck of <10 individuals, ≈10–20 generations ago, accompanied by unprecedented selection coefficients of >0.5 on MHC loci. These results support the importance of balancing selection as a mechanism to maintain variation in natural populations and expose the difficulty of using neutral markers as surrogates for variation in fitness-related loci. PMID:14990802

Sexual reproduction, sporophyte development and molecular variation in the model moss Physcomitrella patens: introducing the ecotype Reute.

PubMed

Hiss, Manuel; Meyberg, Rabea; Westermann, Jens; Haas, Fabian B; Schneider, Lucas; Schallenberg-Rüdinger, Mareike; Ullrich, Kristian K; Rensing, Stefan A

2017-05-01

Rich ecotype collections are used for several plant models to unravel the molecular causes of phenotypic differences, and to investigate the effects of environmental adaption and acclimation. For the model moss Physcomitrella patens collections of accessions are available, and have been used for phylogenetic and taxonomic studies, for example, but few have been investigated further for phenotypic differences. Here, we focus on the Reute accession and provide expression profiling and comparative developmental data for several stages of sporophyte development, as well as information on genetic variation via genomic sequencing. We analysed cross-technology and cross-laboratory data to define a confident set of 15 mature sporophyte-specific genes. We find that the standard laboratory strain Gransden produces fewer sporophytes than Reute or Villersexel, although gametangia develop with the same time course and do not show evident morphological differences. Reute exhibits less genetic variation relative to Gransden than Villersexel, yet we found variation between Gransden and Reute in the expression profiles of several genes, as well as variation hot spots and genes that appear to evolve under positive Darwinian selection. We analyzed expression differences between the ecotypes for selected candidate genes in the GRAS transcription factor family, the chalcone synthase family and in genes involved in cell wall modification that are potentially related to phenotypic differences. We confirm that Reute is a P. patens ecotype, and suggest its use for reverse-genetics studies that involve progression through the life cycle and multiple generations. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

PubMed

Marsden, Clare D; Ortega-Del Vecchyo, Diego; O'Brien, Dennis P; Taylor, Jeremy F; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D; Wayne, Robert K; Lohmueller, Kirk E

2016-01-05

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.

Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs

PubMed Central

Marsden, Clare D.; Ortega-Del Vecchyo, Diego; O’Brien, Dennis P.; Taylor, Jeremy F.; Ramirez, Oscar; Vilà, Carles; Marques-Bonet, Tomas; Schnabel, Robert D.; Wayne, Robert K.; Lohmueller, Kirk E.

2016-01-01

Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2–3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants. PMID:26699508

Genetic differentiation among populations of marine algae

NASA Astrophysics Data System (ADS)

Innes, D. J.

1984-09-01

Most of the information for genetic differentiation among populations of marine algae is from studies on ecotypic variation. Physiological ecotypes have been described for individuals showing different responses to temperature and salinity conditions. Morphological ecotypes have also been found associated with areas differing in wave exposure or different intertidal positions. Little is known on how genetic variation is organized within and between populations of marine algae. The occurrence of ecotypic variation in some species is evidence for genetic differentiation among populations resulting from selection by the local environment. The rate of dispersal and subsequent gene flow will also affect the level of differentiation among populations. In species with low dispersal, differentiation can arise through chance founder events or random genetic drift. The few studies available have shown that species of algae exhibit a range of dispersal capabilities. This information can be useful for predicting the potential level of genetic differentiation among populations of these species. Crossing experiments with several species of algae have shown that populations separated by a considerable distance can be interfertile. In some cases individuals from these populations have been found to be morphologically distinct. Crosses have been used to study the genetic basis of this variation and are evidence for genetic differentiation among the populations sampled. Genetic variation of enzyme proteins detected by electrophoresis provides an additional method for measuring genetic variation within and between populations of marine algae. Electrophoretic methods have previously been used to study systematic problems in algae. However, there have been few attempts to use electrophoretic variation to study the genetic structure of populations of marine algae. This approach is outlined and includes some of the potential problems associated with interpreting electrophoretic data. Studies of electrophoretic variation in natural populations of Enteromorpha linza from Long island Sound are used as an example. This species was found to reproduce only asexually. Despite a dispersing spore stage, genetic differentiation was found on a microgeographic scale and was correlated with differences in the local environment of some of the populations. Similar studies on other species, and especially sexually reproducing species, will add to a growing understanding of the evolutionary genetics of marine algae.

[Genetic variation of geographical provenance of Pinus massoniana--review and analysis].

PubMed

Li, D; Peng, S

2000-04-01

Pinus massoniana is a significant tree species constituting the subtropical forests in China. Based on morphological, physio-ecological, chromosome, and molecular levels, the genetic variation of geographical provenance of P. massoniana and its distribution were reviewed, and the methodologies on genetic diversity and the genetic variation patterns of geographical provenance of P. massoniana were synthetically analyzed. The Key problems on molecular ecology of P. massoniana were discussed.

Quantitative Genetic Architecture at Latitudinal Range Boundaries: Reduced Variation but Higher Trait Independence.

PubMed

Paccard, Antoine; Van Buskirk, Josh; Willi, Yvonne

2016-05-01

Species distribution limits are hypothesized to be caused by small population size and limited genetic variation in ecologically relevant traits, but earlier studies have not evaluated genetic variation in multivariate phenotypes. We asked whether populations at the latitudinal edges of the distribution have altered quantitative genetic architecture of ecologically relevant traits compared with midlatitude populations. We calculated measures of evolutionary potential in nine Arabidopsis lyrata populations spanning the latitudinal range of the species in eastern and midwestern North America. Environments at the latitudinal extremes have reduced water availability, and therefore plants were assessed under wet and dry treatments. We estimated genetic variance-covariance (G-) matrices for 10 traits related to size, development, and water balance. Populations at southern and northern distribution edges had reduced levels of genetic variation across traits, but their G-matrices were more spherical; G-matrix orientation was unrelated to latitude. As a consequence, the predicted short-term response to selection was at least as strong in edge populations as in central populations. These results are consistent with genetic drift eroding variation and reducing the effectiveness of correlational selection at distribution margins. We conclude that genetic variation of isolated traits poorly predicts the capacity to evolve in response to multivariate selection and that the response to selection may frequently be greater than expected at species distribution margins because of genetic drift.

Effects of Genetic Drift and Gene Flow on the Selective Maintenance of Genetic Variation

PubMed Central

Star, Bastiaan; Spencer, Hamish G.

2013-01-01

Explanations for the genetic variation ubiquitous in natural populations are often classified by the population–genetic processes they emphasize: natural selection or mutation and genetic drift. Here we investigate models that incorporate all three processes in a spatially structured population, using what we call a construction approach, simulating finite populations under selection that are bombarded with a steady stream of novel mutations. As expected, the amount of genetic variation compared to previous models that ignored the stochastic effects of drift was reduced, especially for smaller populations and when spatial structure was most profound. By contrast, however, for higher levels of gene flow and larger population sizes, the amount of genetic variation found after many generations was greater than that in simulations without drift. This increased amount of genetic variation is due to the introduction of slightly deleterious alleles by genetic drift and this process is more efficient when migration load is higher. The incorporation of genetic drift also selects for fitness sets that exhibit allele-frequency equilibria with larger domains of attraction: they are “more stable.” Moreover, the finiteness of populations strongly influences levels of local adaptation, selection strength, and the proportion of allele-frequency vectors that can be distinguished from the neutral expectation. PMID:23457235

Multiple capacitors for natural genetic variation in Drosophila melanogaster.

PubMed

Takahashi, Kazuo H

2013-03-01

Cryptic genetic variation (CGV) or a standing genetic variation that is not ordinarily expressed as a phenotype is released when the robustness of organisms is impaired under environmental or genetic perturbations. Evolutionary capacitors modulate the amount of genetic variation exposed to natural selection and hidden cryptically; they have a fundamental effect on the evolvability of traits on evolutionary timescales. In this study, I have demonstrated the effects of multiple genomic regions of Drosophila melanogaster on CGV in wing shape. I examined the effects of 61 genomic deficiencies on quantitative and qualitative natural genetic variation in the wing shape of D. melanogaster. I have identified 10 genomic deficiencies that do not encompass a known candidate evolutionary capacitor, Hsp90, exposing natural CGV differently depending on the location of the deficiencies in the genome. Furthermore, five genomic deficiencies uncovered qualitative CGV in wing morphology. These findings suggest that CGV in wing shape of wild-type D. melanogaster is regulated by multiple capacitors with divergent functions. Future analysis of genes encompassed by these genomic regions would help elucidate novel capacitor genes and better understand the general features of capacitors regarding natural genetic variation. © 2012 Blackwell Publishing Ltd.

Fire alters patterns of genetic diversity among 3 lizard species in Florida Scrub habitat.

PubMed

Schrey, Aaron W; Ashton, Kyle G; Heath, Stacy; McCoy, Earl D; Mushinsky, Henry R

2011-01-01

The Florida Sand Skink (Plestiodon reynoldsi), the Florida Scrub Lizard (Sceloporus woodi), and the Six-lined Racerunner (Aspidoscelis sexlineata) occur in the threatened and fire-maintained Florida scrub habitat. Fire may have different consequences to local genetic diversity of these species because they each have different microhabitat preference. We collected tissue samples of each species from 3 sites with different time-since-fire: Florida Sand Skink n = 73, Florida Scrub Lizard n = 70, and Six-lined Racerunner n = 66. We compared the effect of fire on genetic diversity at microsatellite loci for each species. We screened 8 loci for the Florida Sand Skink, 6 loci for the Florida Scrub Lizard, and 6 loci for the Six-lined Racerunner. We also tested 2 potential driving mechanisms for the observed change in genetic diversity, a metapopulation source/sink model and a local demographic model. Genetic diversity varied with fire history, and significant genetic differentiation occurred among sites. The Florida Scrub Lizard had highest genetic variation at more recently burned sites, whereas the Florida Sand Skink and the Six-lined Racerunner had highest genetic variation at less recently burned sites. Habitat preferences of the Florida Sand Skink and the Florida Scrub Lizard may explain their discordant results, and the Six-lined Racerunner may have a more complicated genetic response to fire or is acted on at a different geographic scale than we have investigated. Our results indicate that these species may respond to fire in a more complicated manner than predicted by our metapopulation model or local demographic model. Our results show that the population-level responses in genetic diversity to fire are species-specific mandating conservation management of habitat diversity through a mosaic of burn frequencies.

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis

PubMed Central

Zwingerman, Nora; Medina-Rivera, Alejandra; Kassam, Irfahan; Wilson, Michael D.; Morange, Pierre-Emmanuel; Trégouët, David-Alexandre; Gagnon, France

2017-01-01

Background Thrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis. Methods A comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models. Results A total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96–1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71–0.97, p = 0.021) for venous thrombosis. Conclusions A comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models. PMID:28552956

Sex-specific effect of CPB2 Ala147Thr but not Thr325Ile variants on the risk of venous thrombosis: A comprehensive meta-analysis.

PubMed

Zwingerman, Nora; Medina-Rivera, Alejandra; Kassam, Irfahan; Wilson, Michael D; Morange, Pierre-Emmanuel; Trégouët, David-Alexandre; Gagnon, France

2017-01-01

Thrombin activatable fibrinolysis inhibitor (TAFI), encoded by the Carboxypeptidase B2 gene (CPB2), is an inhibitor of fibrinolysis and plays a role in the pathogenesis of venous thrombosis. Experimental findings support a functional role of genetic variants in CPB2, while epidemiological studies have been unable to confirm associations with risk of venous thrombosis. Sex-specific effects could underlie the observed inconsistent associations between CPB2 genetic variants and venous thrombosis. A comprehensive literature search was conducted for associations between Ala147Thr and Thr325Ile variants with venous thrombosis. Authors were contacted to provide sex-specific genotype counts from their studies. Combined and sex-specific random effects meta-analyses were used to estimate a pooled effect estimate for primary and secondary genetic models. A total of 17 studies met the inclusion criteria. A sex-specific meta-analysis applying a dominant model supported a protective effect of Ala147Thr on venous thrombosis in females (OR = 0.81, 95%CI: 0.68,0.97; p = 0.018), but not in males (OR = 1.06, 95%CI:0.96-1.16; p = 0.263). The Thr325Ile did not show a sex-specific effect but showed variation in allele frequencies by geographic region. A subgroup analysis of studies in European countries showed decreased risk, with a recessive model (OR = 0.83, 95%CI:0.71-0.97, p = 0.021) for venous thrombosis. A comprehensive literature review, including unpublished data, provided greater statistical power for the analyses and decreased the likelihood of publication bias influencing the results. Sex-specific analyses explained apparent discrepancies across genetic studies of Ala147Thr and venous thrombosis. While, careful selection of genetic models based on population genetics, evolutionary and biological knowledge can increase power by decreasing the need to adjust for testing multiple models.

Genetics of eosinophilic esophagitis

PubMed Central

Kottyan, LC; Rothenberg, ME

2017-01-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches. PMID:28224995

Genetics of eosinophilic esophagitis.

PubMed

Kottyan, L C; Rothenberg, M E

2017-05-01

Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE. We will also discuss the clinical opportunities that genetic analyses provide in the form of decision support tools, molecular diagnostics, and novel therapeutic approaches.

Genetic depletion at adaptive but not neutral loci in an endangered bird species.

PubMed

Hartmann, Stefanie A; Schaefer, H Martin; Segelbacher, Gernot

2014-12-01

Many endangered species suffer from the loss of genetic diversity, but some populations may be able to thrive even if genetically depleted. To investigate the underlying genetic processes of population bottlenecks, we apply an innovative approach for assessing genetic diversity in the last known population of the endangered Pale-headed Brushfinch (Atlapetes pallidiceps) in Ecuador. First, we measure genetic diversity at eleven neutral microsatellite loci and adaptive SNP variation in five Toll-like receptor (TLR) immune system genes. Bottleneck tests confirm genetic drift as the main force shaping genetic diversity in this species and indicate a 99 % reduction in population size dating back several hundred years. Second, we compare contemporary microsatellite diversity with historic museum samples of A. pallidiceps, finding no change in genetic diversity. Third, we compare genetic diversity in the Pale-headed Brushfinch with two co-occurring-related brushfinch species (Atlapetes latinuchus, Buarremon torquatus), finding a reduction of up to 91% diversity in the immune system genes but not in microsatellites. High TLR diversity is linked to decreased survival probabilities in A. pallidiceps. Low TLR diversity is thus probably an adaptation to the specific selection regime within its currently very restricted distribution (approximately 200 ha), but could severely restrict the adaptive potential of the species in the long run. Our study illustrates the importance of investigating both neutral and adaptive markers to assess the effect of population bottlenecks and for recommending specific management plans in endangered species. © 2014 John Wiley & Sons Ltd.

Broad Bandwidth or High Fidelity? Evidence from the Structure of Genetic and Environmental Effects on the Facets of the Five Factor Model

PubMed Central

Briley, Daniel A.; Tucker-Drob, Elliot M.

2017-01-01

The Five Factor Model (FFM) of personality is well-established at the phenotypic level, but much less is known about the coherence of the genetic and environmental influences within each personality domain. Univariate behavioral genetic analyses have consistently found the influence of additive genes and nonshared environment on multiple personality facets, but the extent to which genetic and environmental influences on specific facets reflect more general influences on higher order factors is less clear. We applied a multivariate quantitative-genetic approach to scores on the CPI-Big Five facets for 490 monozygotic and 317 dizygotic twins who took part in the National Merit Twin Study. Our results revealed a complex genetic structure for facets composing all five factors, with both domain-general and facet-specific genetic and environmental influences. Models that required common genetic and environmental influences on each facet to occur by way of effects on a higher order trait did not fit as well as models allowing for common genetic and environmental effects to act directly on the facets for three of the Big Five domains. These results add to the growing body of literature indicating that important variation in personality occurs at the facet level which may be overshadowed by aggregating to the trait level. Research at the facet level, rather than the factor level, is likely to have pragmatic advantages in future research on the genetics of personality. PMID:22695681

Human leukocyte antigen and cytokine receptor gene polymorphisms associated with heterogeneous immune responses to mumps viral vaccine.

PubMed

Ovsyannikova, Inna G; Jacobson, Robert M; Dhiman, Neelam; Vierkant, Robert A; Pankratz, V Shane; Poland, Gregory A

2008-05-01

Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine. To identify genetic factors that might contribute to variations in mumps vaccine-induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12-18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children. Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination. These data suggest the important role of HLA and immunoregulatory cytokine receptor gene polymorphisms in explaining variations in mumps vaccine-induced immune responses.

Human Leukocyte Antigen and Cytokine Receptor Gene Polymorphisms Associated With Heterogeneous Immune Responses to Mumps Viral Vaccine

PubMed Central

Ovsyannikova, Inna G.; Jacobson, Robert M.; Dhiman, Neelam; Vierkant, Robert A.; Pankratz, V. Shane; Poland, Gregory A.

2009-01-01

OBJECTIVES Mumps outbreaks continue to occur throughout the world, including in highly vaccinated populations. Vaccination against mumps has been successful; however, humoral and cellular immune responses to mumps vaccines vary significantly from person to person. We set out to assess whether HLA and cytokine gene polymorphisms are associated with variations in the immune response to mumps viral vaccine. METHODS To identify genetic factors that might contribute to variations in mumps vaccine–induced immune responses, we performed HLA genotyping in a group of 346 healthy schoolchildren (12–18 years of age) who previously received 2 doses of live mumps vaccine. Single-nucleotide polymorphisms (minor allele frequency of >5%) in cytokine and cytokine receptor genes were genotyped for a subset of 118 children. RESULTS Median values for mumps-specific antibody titers and lymphoproliferative stimulation indices were 729 IU/mL and 4.8, respectively. Girls demonstrated significantly higher mumps antibody titers than boys, indicating gender-linked genetic differences in humoral immune response. Significant associations were found between the HLA-DQB1*0303 alleles and lower mumps-specific antibody titers. An interesting finding was the association of several HLA class II alleles with mumps-specific lymphoproliferation. Alleles of the DRB1 (*0101, *0301, *0801, *1001, *1201, and *1302), DQA1 (*0101, *0105, *0401, and *0501), and DQB1 (*0201, *0402, and *0501) loci were associated with significant variations in lymphoproliferative immune responses to mumps vaccine. Additional associations were observed with single-nucleotide polymorphisms in the interleukin-10RA, interleukin-12RB1, and interleukin-12RB2 cytokine receptor genes. Minor alleles for 4 single-nucleotide polymorphisms within interleukin-10RA and interleukin-12RB genes were associated with variations in humoral and cellular immune responses to mumps vaccination. CONCLUSIONS These data suggest the important role of HLA and immunoregulatory cytokine receptor gene polymorphisms in explaining variations in mumps vaccine–induced immune responses. PMID:18450852

Extensive genetic and DNA methylation variation contribute to heterosis in triploid loquat hybrids.

PubMed

Liu, Chao; Wang, Mingbo; Wang, Lingli; Guo, Qigao; Liang, Guolu

2018-04-24

We aim to overcome the unclear origin of the loquat and elucidate the heterosis mechanism of the triploid loquat. Here we investigated the genetic and epigenetic variations between the triploid plant and its parental lines using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplified fragment length polymorphism (MSAP) analyses. We show that in addition to genetic variations, extensive DNA methylation variation occurred during the formation process of triploid loquat, with the triploid hybrid having increased DNA methylation compared to the parents. Furthermore, a correlation existed between genetic variation and DNA methylation remodeling, suggesting that genome instability may lead to DNA methylation variation or vice versa. Sequence analysis of the MSAP bands revealed that over 53% of them overlap with protein-coding genes, which may indicate a functional role of the differential DNA methylation in gene regulation and hence heterosis phenotypes. Consistent with this, the genetic and epigenetic alterations were associated closely to the heterosis phenotypes of triploid loquat, and this association varied for different traits. Our results suggested that the formation of triploid is accompanied by extensive genetic and DNA methylation variation, and these changes contribute to the heterosis phenotypes of the triploid loquats from the two cross lines.

Natural genetic variation of root system architecture from Arabidopsis to Brachypodium: towards adaptive value.

PubMed

Pacheco-Villalobos, David; Hardtke, Christian S

2012-06-05

Root system architecture is a trait that displays considerable plasticity because of its sensitivity to environmental stimuli. Nevertheless, to a significant degree it is genetically constrained as suggested by surveys of its natural genetic variation. A few regulators of root system architecture have been isolated as quantitative trait loci through the natural variation approach in the dicotyledon model, Arabidopsis. This provides proof of principle that allelic variation for root system architecture traits exists, is genetically tractable, and might be exploited for crop breeding. Beyond Arabidopsis, Brachypodium could serve as both a credible and experimentally accessible model for root system architecture variation in monocotyledons, as suggested by first glimpses of the different root morphologies of Brachypodium accessions. Whether a direct knowledge transfer gained from molecular model system studies will work in practice remains unclear however, because of a lack of comprehensive understanding of root system physiology in the native context. For instance, apart from a few notable exceptions, the adaptive value of genetic variation in root system modulators is unknown. Future studies should thus aim at comprehensive characterization of the role of genetic players in root system architecture variation by taking into account the native environmental conditions, in particular soil characteristics.

Genetic variation, multiple paternity, and measures of reproductive success in the critically endangered hawksbill turtle (Eretmochelys imbricata).

PubMed

González-Garza, Blanca Idalia; Stow, Adam; Sánchez-Teyer, Lorenzo Felipe; Zapata-Pérez, Omar

2015-12-01

The Yucatán Peninsula in Mexico contains some of the largest breeding groups of the globally distributed and critically endangered hawksbill turtle (Eretmochelys imbricata). An improved understanding of the breeding system of this species and how its genetic variation is structured among nesting areas is required before the threats to its survival can be properly evaluated. Here, we genotype 1195 hatchlings and 41 nesting females at 12 microsatellite loci to assess levels of multiple paternity, genetic variation and whether individual levels of homozygosity are associated with reproductive success. Of the 50 clutches analyzed, only 6% have multiple paternity. The distribution of pairwise relatedness among nesting localities (rookeries) was not random with elevated within-rookery relatedness, and declining relatedness with geographic distance indicating some natal philopatry. Although there was no strong evidence that particular rookeries had lost allelic variation via drift, younger turtles had significantly lower levels of genetic variation than older turtles, suggesting some loss of genetic variation. At present there is no indication that levels of genetic variation are associated with measures of reproductive success such as clutch size, hatching success, and frequency of infertile eggs.

Beyond Biodiversity: Fish Metagenomes

PubMed Central

Ardura, Alba; Planes, Serge; Garcia-Vazquez, Eva

2011-01-01

Biodiversity and intra-specific genetic diversity are interrelated and determine the potential of a community to survive and evolve. Both are considered together in Prokaryote communities treated as metagenomes or ensembles of functional variants beyond species limits. Many factors alter biodiversity in higher Eukaryote communities, and human exploitation can be one of the most important for some groups of plants and animals. For example, fisheries can modify both biodiversity and genetic diversity (intra specific). Intra-specific diversity can be drastically altered by overfishing. Intense fishing pressure on one stock may imply extinction of some genetic variants and subsequent loss of intra-specific diversity. The objective of this study was to apply a metagenome approach to fish communities and explore its value for rapid evaluation of biodiversity and genetic diversity at community level. Here we have applied the metagenome approach employing the Barcoding target gene COI as a model sequence in catch from four very different fish assemblages exploited by fisheries: freshwater communities from the Amazon River and northern Spanish rivers, and marine communities from the Cantabric and Mediterranean seas. Treating all sequences obtained from each regional catch as a biological unit (exploited community) we found that metagenomic diversity indices of the Amazonian catch sample here examined were lower than expected. Reduced diversity could be explained, at least partially, by overexploitation of the fish community that had been independently estimated by other methods. We propose using a metagenome approach for estimating diversity in Eukaryote communities and early evaluating genetic variation losses at multi-species level. PMID:21829636

Beyond biodiversity: fish metagenomes.

PubMed

Ardura, Alba; Planes, Serge; Garcia-Vazquez, Eva

2011-01-01

Biodiversity and intra-specific genetic diversity are interrelated and determine the potential of a community to survive and evolve. Both are considered together in Prokaryote communities treated as metagenomes or ensembles of functional variants beyond species limits.Many factors alter biodiversity in higher Eukaryote communities, and human exploitation can be one of the most important for some groups of plants and animals. For example, fisheries can modify both biodiversity and genetic diversity (intra specific). Intra-specific diversity can be drastically altered by overfishing. Intense fishing pressure on one stock may imply extinction of some genetic variants and subsequent loss of intra-specific diversity. The objective of this study was to apply a metagenome approach to fish communities and explore its value for rapid evaluation of biodiversity and genetic diversity at community level. Here we have applied the metagenome approach employing the barcoding target gene coi as a model sequence in catch from four very different fish assemblages exploited by fisheries: freshwater communities from the Amazon River and northern Spanish rivers, and marine communities from the Cantabric and Mediterranean seas.Treating all sequences obtained from each regional catch as a biological unit (exploited community) we found that metagenomic diversity indices of the Amazonian catch sample here examined were lower than expected. Reduced diversity could be explained, at least partially, by overexploitation of the fish community that had been independently estimated by other methods.We propose using a metagenome approach for estimating diversity in Eukaryote communities and early evaluating genetic variation losses at multi-species level.

Spatial and Temporal Dynamics of Pacific Oyster Hemolymph Microbiota across Multiple Scales

PubMed Central

Lokmer, Ana; Goedknegt, M. Anouk; Thieltges, David W.; Fiorentino, Dario; Kuenzel, Sven; Baines, John F.; Wegner, K. Mathias

2016-01-01

Unveiling the factors and processes that shape the dynamics of host associated microbial communities (microbiota) under natural conditions is an important part of understanding and predicting an organism's response to a changing environment. The microbiota is shaped by host (i.e., genetic) factors as well as by the biotic and abiotic environment. Studying natural variation of microbial community composition in multiple host genetic backgrounds across spatial as well as temporal scales represents a means to untangle this complex interplay. Here, we combined a spatially-stratified with a longitudinal sampling scheme within differentiated host genetic backgrounds by reciprocally transplanting Pacific oysters between two sites in the Wadden Sea (Sylt and Texel). To further differentiate contingent site from host genetic effects, we repeatedly sampled the same individuals over a summer season to examine structure, diversity and dynamics of individual hemolymph microbiota following experimental removal of resident microbiota by antibiotic treatment. While a large proportion of microbiome variation could be attributed to immediate environmental conditions, we observed persistent effects of antibiotic treatment and translocation suggesting that hemolymph microbial community dynamics is subject to within-microbiome interactions and host population specific factors. In addition, the analysis of spatial variation revealed that the within-site microenvironmental heterogeneity resulted in high small-scale variability, as opposed to large-scale (between-site) stability. Similarly, considerable within-individual temporal variability was in contrast with the overall temporal stability at the site level. Overall, our longitudinal, spatially-stratified sampling design revealed that variation in hemolymph microbiota is strongly influenced by site and immediate environmental conditions, whereas internal microbiome dynamics and oyster-related factors add to their long-term stability. The combination of small and large scale resolution of spatial and temporal observations therefore represents a crucial but underused tool to study host-associated microbiome dynamics. PMID:27630625

Comparative Population Genomics Analysis of the Mammalian Fungal Pathogen Pneumocystis.

PubMed

Cissé, Ousmane H; Ma, Liang; Wei Huang, Da; Khil, Pavel P; Dekker, John P; Kutty, Geetha; Bishop, Lisa; Liu, Yueqin; Deng, Xilong; Hauser, Philippe M; Pagni, Marco; Hirsch, Vanessa; Lempicki, Richard A; Stajich, Jason E; Cuomo, Christina A; Kovacs, Joseph A

2018-05-08

Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro Human Pneumocystis infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of Pneumocystis infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that Pneumocystis species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of Pneumocystis populations during their spread across mammals. IMPORTANCE Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. Pneumocystis , a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, Pneumocystis can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different Pneumocystis species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that Pneumocystis may have undergone recent host shifts. The results demonstrate that Pneumocystis strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.